Systems and methods for stimulation-related volume analysis, creation, and sharing with integrated surgical planning and stimulation programming

ABSTRACT

A computer implemented system and method facilitates a cycle of generation, sharing, and refinement of volumes related to stimulation of anatomical tissue, such as brain or spinal cord stimulation. Such volumes can include target stimulation volumes, side effect volumes, and volumes of estimated activation. A computer system and method also facilitates analysis of groups of volumes, including analysis of differences and/or commonalities between different groups of volumes.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit under 35 U.S.C. § 119(e) of U.S.Provisional Patent Application Ser. No. 62/031,075, which is herebyincorporated herein by reference in its entirety.

FIELD OF THE INVENTION

Aspects of the present invention pertain to management of data in acentral location for access at multiple locations, by various machines,and via various applications. Aspects of the present invention pertainto an interface of a stimulation setting remote control in a clinicalmode. Aspects of the present invention pertain to sharing of targetvolumes of activation.

BACKGROUND

Electrical stimulation of an anatomical region, e.g., deep brainstimulation (DBS), such as of the thalamus or basal ganglia, is aclinical technique for the treatment of disorders such as essentialtremor, Parkinson's disease (PD), and other physiological disorders. DBSmay also be useful for traumatic brain injury and stroke. Pilot studieshave also begun to examine the utility of DBS for treating dystonia,epilepsy, and obsessive-compulsive disorder.

A stimulation procedure, such as DBS, typically involves first obtainingpreoperative images. e.g., of the patient's brain, such as by using acomputed tomography (CT) scanner device, a magnetic resonance imaging(MRI) device, or any other imaging modality. This sometimes involvesfirst affixing to the patient's skull spherical or other fiducialmarkers that are visible on the images produced by the imaging modality.The fiducial markers help register the preoperative images to the actualphysical position of the patient in the operating room during the latersurgical procedure.

After the preoperative images are acquired by the imaging modality, theyare then loaded onto an image-guided surgical (IGS) workstation, and,using the preoperative images displayed on the IGS workstation, aneurosurgeon can select a target region, e.g., within the brain, anentry point, e.g., on the patient's skull, and a desired trajectorybetween the entry point and the target region. The entry point andtrajectory are typically carefully selected to avoid intersecting orotherwise damaging certain nearby critical structures or vasculature.e.g., of the brain.

In the operating room, the physician marks the entry point on thepatient's skull, drills a burr hole at that location, and affixes atrajectory guide device about the burr hole. The trajectory guide deviceincludes a bore that can be aimed to obtain the desired trajectory tothe target region. After aiming, the trajectory guide is locked topreserve the aimed trajectory toward the target region. After the aimedtrajectory has been locked in using the trajectory guide, a microdriveintroducer is used to insert the surgical instrument along thetrajectory toward the target region. e.g., of the brain. The surgicalinstrument may include, among other things, a recording electrodeleadwire, for recording intrinsic electrical signals. e.g., of thebrain; a stimulation electrode leadwire, for providing electrical energyto the target region. e.g., of the brain; or associated auxiliaryguidewires or guide catheters for steering a primary instrument towardthe target region. e.g., of the brain.

The stimulation electrode leadwire, which typically includes multipleclosely-spaced electrically independent stimulation electrode contacts,is then introduced to deliver the therapeutic stimulation to the targetregion, e.g., of the brain. The stimulation electrode leadwire is thenimmobilized, such as by using an instrument immobilization devicelocated at the burr hole entry, e.g., in the patient's skull, in orderfor the DBS therapy to be subsequently performed.

The subthalamic nucleus (STN) represents the most common target for DBStechnology. Clinically effective STN DBS for PD has typically usedelectrode contacts in the anterior-dorsal STN. However. STN DBS exhibitsa low threshold for certain undesirable side effects, such as tetanicmuscle contraction, speech disturbance and ocular deviation. Highlyanisotropic fiber tracks are located about the STN. Such nerve tracksexhibit high electrical conductivity in a particular direction.Activation of these tracks has been implicated in many of the DBS sideeffects. However, there exists a limited understanding of the neuralresponse to DBS. The three-dimensional (3-D) tissue medium near the DBSelectrode typically includes both inhomogeneous and anisotropiccharacteristics. Such complexity makes it difficult to predict theparticular volume of tissue influenced by DBS.

After the immobilization of the stimulation electrode leadwire, theactual stimulation therapy is often not initiated until after a timeperiod of about two-weeks to one month has elapsed. This is dueprimarily to the acute reaction of the brain tissue to the introducedelectrode leadwire (e.g., the formation of adjacent scar tissue), andstabilization of the patient's disease symptoms. At that time, aparticular one or more of the stimulation electrode contacts is selectedfor delivering the therapeutic stimulation, and other stimulationparameters are adjusted to achieve an acceptable level of therapeuticbenefit.

A system and method may estimate stimulation volumes, and display modelsof a patient anatomy and/or a stimulation leadwire, via which tographically identify the estimated stimulation volumes and how theyinteract with various regions of the patient anatomy.

The systems and methods may be used to explore target regions ofstimulation and stimulation therapies to determine which therapy regimenis best suited for a particular patient or group of patients.

SUMMARY

Such exploration may result in much data over time for a particularpatient and/or for a patient population. Example embodiments of thepresent invention provide a system and methods to improve the quality ofsuch data, to manage such data, and to maximize use of, and facilitateefficient use of, such information.

The data may pertain to, for example, stimulation of a patient for deepbrain stimulation (DBS) therapy and/or spinal cord stimulation (SCS)therapy. It may include graphical information, such as estimated volumesof activation (VOA), also referred to herein as a stimulation fieldmodel (SFM). It may include information used for rendering the SFMs,such as image registration and/or leadwire location data. It may furtherinclude information regarding the patient's condition, such as diseaseand medications taken, and/or reactions to an applied therapy. It mayfurther include information concerning stimulation programs applied tothe patient for the patient therapy. It may include target volumesselected for a patient, and/or volumes of estimated activation (VOA) forvarious stimulation parameters input for the patient. It may includeinformation concerning how close the patient's anatomical images matchto a standard atlas. It may further include analytics information asdescribed below.

Various systems, system components, and/or program modules may be usedfor performance of various tasks associated with, or that provide anoutput usable for, providing therapeutic stimulation, generation of dataregarding a therapy, and access to and transfer of therapy data.Embodiments of the present invention provide for communication and/orbetween the various systems, system components, and/or program modules.

The various methods described herein may be practiced, each alone, or invarious combinations.

An example embodiment of the present invention is directed to aprocessor, which may be implemented using any conventional processingcircuit and device or combination thereof. e.g., a Central ProcessingUnit (CPU) of a Personal Computer (PC) or other workstation processor,to execute code provided, e.g., on a hardware computer-readable mediumincluding any conventional memory device, to perform any of the methodsdescribed herein, alone or in combination. In certain exampleembodiments, the processor may be embodied in a remote control device.The memory device may include any conventional permanent and/ortemporary memory circuits or combination thereof, a non-exhaustive listof which includes Random Access Memory (RAM), Read Only Memory (ROM).Compact Disks (CD). Digital Versatile Disk (DVD), and magnetic tape.

An example embodiment of the present invention is directed to a hardwarecomputer-readable medium. e.g., as described above, having storedthereon instructions executable by a processor to perform the methodsdescribed herein.

An example embodiment of the present invention is directed to a method,e.g., of a hardware component or machine, of transmitting instructionsexecutable by a processor to perform the methods described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a remote control device according to an exampleembodiment of the present invention.

FIG. 2 shows connections between a remote control device and othersystem components according to an example embodiment of the presentinvention.

FIG. 3 shows connections between a remote control device and othersystem components according to another example embodiment of the presentinvention, aspects of the different illustrated embodiments beingcombinable.

FIG. 4 is a flowchart that illustrates a computer-implemented method ofrefining target volume selection. e.g., over time, according to anexample embodiment of the present invention.

FIG. 5 is an example strength/duration curve plotting differentcombinations of power and pulse width values estimated to provideequivalent stimulation, according to an example embodiment of thepresent invention.

FIG. 6 is a diagram that illustrates a stimulation and analysis cycle bywhich target volumes and/or stimulation settings can be refined,according to an example embodiment of the present invention.

FIG. 7 is a diagram that illustrates a stimulation and analysis cyclewith volume sharing, according to an example embodiment of the presentinvention.

FIG. 8 illustrates a data flow including volume sharing, according to anexample embodiment of the present invention.

FIG. 9 illustrates components usable for representing an anatomicalvolume, according to an example embodiment of the present invention.

FIG. 10 illustrates generation of a patient-specific atlas based onclustering of sub-sets of a patient population based on clinical effectsinformation associated with VOAs of the patient population, according toan example embodiment of the present invention.

FIG. 11 illustrates an example of a trajectory between a current VOA andan optimal VOA, according to an example embodiment of the presentinvention.

FIG. 12 shows an example of a neighborhood effects map, according to anexample embodiment of the present invention.

FIG. 13 illustrates a cloud management paradigm with integration of ahospital image system. e.g., picture archiving and communication system(PACS), patient record system including information on patientassessments, a patient programming system, and a patient analyticssystem, according to an example embodiment of the present invention.

FIG. 14 illustrates a paradigm in which surgical planning, stimulationprogramming/planning, and analytics modules are integrated, according toan example embodiment of the present invention.

FIG. 15 is a further illustration of cloud integration of variousmodules, according to an example embodiment of the present invention.

DETAILED DESCRIPTION

Aspects of the present invention pertain to management of data in acentral location for access at multiple locations, by various machines,and via various applications. Aspects of the present invention pertainto an interface of a stimulation setting remote control in a clinicalmode. Aspects of the present invention pertain to sharing of targetvolumes of activation. The applications and systems via which thevarious data is created and/or accessed and/or used and/or in which thedescribed interfaces may be presented may include any one of thosedescribed in U.S. patent application Ser. No. 12/454,330, filed May 15,2009 (“the '330 application”), U.S. patent application Ser. No.12/454,312, filed May 15, 2009 (“the '312 application”). U.S. patentapplication Ser. No. 12/454,340, filed May 15, 2009 (“the '340application”). U.S. patent application Ser. No. 12/454,343, filed May15, 2009 (“the '343 application”). U.S. patent application Ser. No.12/454,314, filed May 15, 2009 (“the '314 application”). U.S.Provisional Pat. App. Ser. No. 61/468,884, filed Mar. 29, 2011 (“the'884 application”). U.S. Provisional Pat. App. Ser. No. 61/468,887,filed Mar. 29, 2011 (“the '887 application”), U.S. Provisional Pat. App.Ser. No. 61/468,891, filed Mar. 29, 2011 (“the '891 application”), U.S.Provisional Pat. App. Ser. No. 61/468,897, filed Mar. 29, 2011 (“the'897 application”), and U.S. Provisional Pat. App. Ser. No. 61/468,901,filed Mar. 29, 2011 (“the '901 application”), the content of each ofwhich is hereby incorporated herein by reference in its entirety.

Aspects of the present application pertain to subject matter describedin U.S. patent application Ser. Nos. 13/571,078 and 13/570,998, thecontent of both of which were filed Aug. 9, 2012 and are herebyincorporated by reference herein in their entireties. Aspects of thepresent invention also pertain to subject matter described in U.S.Provisional Patent Application Ser. Nos. 61/521,626 filed on Aug. 9,2011, 61/521,641 filed on Aug. 9, 2011, 61/521,632 filed on Aug. 9,2011, 61/676,000 filed on Jul. 26, 2012 and 61/676,014 filed on Jul. 26,2012, the content of all of which are hereby incorporated by referenceherein in their entireties.

Aspects of the present application also pertain to subject matterdescribed in U.S. patent application Ser. No. 13/431,232 (“the '232application) filed Mar. 27, 2012, which claims priority to U.S. Prov.Pat. App. Ser. Nos. 61/468,884, 61/468,887, 61/468,891, 61/468,897, and61/468,901 which were all filed Mar. 29, 2011. The contents of each ofthese applications are also incorporated by reference herein in theirentireties.

Cloud Data Management

A Guide software for stimulation therapy may require various data usedat various points of time. Example embodiments of the present inventionprovide for getting the information to go to the right place at theright time. Additionally, example embodiments allow for patient data totravel with the patient. Information may include the graphics, but mayalso include other non-imagery data, as noted above, such as sideeffects, tremors (e.g., measured by an accelerometer in the implantablepulse generator (IPG)), medications, and other clinical data that may beupdated over time.

In an example embodiment of the present invention, a patient can beassigned and given an identification (ID) card that has the patient'sdata. For example, the card may be inserted into, or otherwise beprovided in communication with, a computer and data on the computer maybe recorded on the card. However, as explained in connection with thealternative embodiments below, the data need not be stored on the card,and the card would then only be used for obtaining access to the data,which can be stored remotely, for example, in a central server.

In an alternative example embodiment, the patient has a card thatincludes a pin number that one can use to access the patient'sinformation.

In an alternative example embodiment, the patient has a card thatincludes an account number that, when input to a computer along with apin number from the user's memory, allows access to the patient'sinformation.

In an alternative example embodiment, the card includes a number that,when the card is swiped in a device connected to a computer, is read bythe computer, and that thereby allows access to the data of the patientassociated with the number. In an example embodiment, the number can beone on the patient's implanted IPG, which is already managed to haveunique numbers. Use of such a number, rather than patient name, can helpwith anonymization issues. That is, the data is stored in connectionwith a number, rather than in association with data by which canidentify the patient.

A problem is where data is recorded before the user obtains the IPG. Inthis instance, a temporary number may be assigned, and then, when theIPG is implanted, a switchover may be made to the number of the IPG.

Use of the IPG number may be advantageous because even if the user losesthe card, the user can obtain the information by using the IPG whichobviously does not get lost.

In an example embodiment of the present information the IPG may transmita signal with the number. According to this embodiment, the card may beomitted. Instead, the signal of the IPG indicating the unique number (orany unique signal that may be omitted by the IPG which unique signal isassociated with the particular patient) may allow the data access. Notonly the IPG, but any RFID device provided to the user can be used toprovide the number. However, it is preferred to use a device implantedin the patient, so that it is ensured not to be lost.

The computer may “talk” to the signaling device on the patient to getthe number needed to obtain (or send to the server) the information. Forexample, the user may connect a device to a port of a computer (e.g., aUSB port, a serial port or any other communications port), which deviceis configured to receive a signal from the IPG, which indicates somenumber. The number is sent to the central server and then theinformation is obtained. This can be beneficial for security purposes aswell because it allows the system to be controlled not to send theinformation unless the device recognizes that the patient with thecorrect IPG is physically present at the computer terminal at which theinformation is being requested or via which information is being stored.

The guide system, including the visualization package, the clinicianprogrammer (CP) by which the clinician actually programs the IPG, or thepatient programmer system by which the IPG settings can be changedwithout the clinician, and the analytic system (described below) caneach access the information in the cloud. In an example embodiment, anyweb browser may be used to access the information.

Different users can have different types of access. For example, apatient may have a certain level of access, a health care provider mayhave another level of access, and a relative (who is not the health careprovider) can have yet another level of access.

In an example embodiment, the IPG may be programmed to generate, basedon a user-input code, a second code that provides a specific level ofaccess. The second code may be unique to the user (e.g., a particularhealth care provider). In this manner, different levels of access may beprovided to data generated using the same IPG. Thus, for example, ahealth care provider may only be able to access IPG data generated atthe provider's facility, but may not have access to IPG data generatedat other provider facilities, even though the IPG is the same.

In an example embodiment, health care providers may be provided with theability to access the data without the patient (and therefore the IPG)being physically present. For example, the provider may store thepatient's access credentials (e.g., IPG number) the first time thepatient visits, so that patient data can be obtained prior to the nextvisit.

Additional data that can be included in the central location for accessas described above is analytics information as described below and thedata used for the analytics.

Additional information stored in the cloud can be a log of the changesentered by the patients to their parameters using the remote control,which changes could be time-stamped, as described below. The remotecontrol will record the information. The remote control can be pluggedinto a computer which then sends it to the central location for storagein association with the number that is unique to the patient.Alternatively, it can be sent continuously or periodically through,e.g., a wireless connection, e.g., via a cellular connection.Alternatively, the remote control can connect to a device through awireless connection, and, when so connected, it can send the informationto the central server.

Additionally, the detailed computations—fusion of MR/CT, fusion of atlasto MR, lead location, VOA generation, etc. (see all computations anddata described in the '330, '312, '340, '343, '314, '884. '887. '891,'897, and '901 applications)—can be performed at a server and theresulting information can be stored centrally.

In an example embodiment, transformation matrix parameters can be storedcentrally. For example, the central server, the IPG, and/or the remoteused by the patient would store the transformation matrices, such as howto transform the atlas to the patient's MR. Additionally, it could storethe location of the lead in the resulting patient-specific atlas. Itcould also store an atlas identifier to identify which atlas is the onebeing transformed, in case different atlases are used at differenttimes, e.g., because of a software upgrade.

In an example embodiment of the present invention, information fromsensors monitoring a patient condition, for example, while stimulationis being performed, immediately thereafter, or during a longer periodspanning a stimulation therapy including periods of on and offstimulation states, is uploaded to a cloud data store which isaccessible by clinicians, doctors, and/or the patient logging intovarious stimulation control modules, e.g., a stimulation programmingand/or planning module. According to an example embodiment, the sensorinformation is associated with VOAs as further described below which isused for patient population analytics, as further described below.

FIG. 13 illustrates a cloud management paradigm with integration of ahospital image system. e.g., picture archiving and communication system(PACS) 1310, patient record system including information on patientassessments 1311, a patient programming system, and a patient analyticssystem. Patient records, including assessments are uploadable to acentral cloud data store 1312. Patient images are also uploadable fromthe PACS system to the cloud data store. Data analytics 1314 asdescribed below are also uploadable to the cloud 1312. The cloud mayinclude a server which maintains programs accessible from terminals,e.g., over the Internet, for determining lead trajectories for surgicalplanning based on the patient images and patient assessment information.The programs can also include ones usable for registering a lead modelto a patient atlas, e.g., after the lead has been implanted. The cloudcan further include programs used for planning stimulation programs, andfor actually programming the implanted pulse generator (IPG). A smartphone 1316 can be used to access these programs. A stimulation bridge1318, which can be embodied in a dongle, can interface between the IPG1320 and the stimulation programming module for programming the IPG tocause the implanted leadwire to generate electrical pulses according tothe program. Information concerning the effects of the stimulation canbe obtained automatically and/or manually input, e.g., via a patientinterface module, which can also be accessible from the cloud to updatethe analytics information. The effects information are correlated withthe stimulation program set in the programming module and for which theprogram planning module generates estimated VOAs.

Data Export/Import

According to an example embodiment of the present invention, a samestimulation-related and/or anatomical atlas (patient-specific ornon-patient-specific) data can be accessed via multiple computerterminals. For example, in an example embodiment, such data is saved toa file stored at a central location accessible from multiple computerterminals.

In an example embodiment of the present invention, such data can beshared with other users, e.g., as an attachment to a communication(e.g., an e-mail) or by providing the other user access to the centrallystored file. Such data often includes information that is specific to apatient and private. Accordingly, in an example embodiment of thepresent invention, the system includes an anonymization feature forstripping from the shared data any data that identifies the patients.For example, in an example embodiment, the system includes a soft orhard selectable button, in response to selection of which the systemstrips private data. For example, the system can be programmed to removepatient name, address, social security, etc. In an example embodiment,in response to selection of the anonymization button, the system outputsa list of types of data which the user can select to strip. In analternative example embodiment, the system saves the informationcentrally with all of the data, and depending on permissions set for auser attempting to access the centrally stored data, either provides thedata with the private information or provides a stripped-down version ofthe data.

According to an example embodiment of the present invention, the systemis configured to transmit VOAs or other volumes in the form of centroids(e.g., center of mass of the volume). e.g., in combination with otherelliptically based information, as further described below. In anexample embodiment, volumes can be transmitted/opened in a CAD format.Volumes can be exported to other users in the reference frame of thepatient for whom the volume was generated. Alternatively, the volume canbe transformed to a common reference frame, e.g., a common atlas, andtransmitted to other users in this generic form. In an exampleembodiment, the system is configured to export the VOA or other volumeas a full 3D mesh of the volume.

In an example embodiment, the system is configured to export geometricprimitives of the volumes, e.g., of the VOAs. For example, in an exampleembodiment, the system saves/transmits the parameters of a sphere orellipse that best matches the VOA, which allows for the amount of datathat is to be saved and/or exported to be scaled down. Such data can besent, for example, in an Excel format, as a comma delimited file, as atext file, or as a CAD file. Providing the volume information in suchforms can be beneficial to allow one to use third party applications notadapted to interpret/process the more intricate volume data the Guidesoftware is configured to process.

For example, a volume. e.g., a VOA, can be saved/transmitted as a set ofpoints in 3D space with information on how those points are connected.Alternatively, the volume can be saved as a combination of a centroidand, for example, a radius. The radius can be that which is determinedto provide an ellipse that optimally overlaps the volume. e.g., withleast combined difference of overlap and underlap to the volume or thesmallest ellipse that covers all points of the volume. For example, thesystem can store a plurality of volumes, each as a row including thedata {x, y, z, r}, where x,y,z represent a point in three-dimensionalspace at a center of mass of the volume and r represents the radius.

According to a variant of this embodiment, the system can includemultiple radii to represent the volume, for example, to represent athree-dimensional ellipsoid. For example, three radii r1, r2, r3 can beused, each for a respective one of the x, y, and z directions, as shownin FIG. 9. In an example embodiment of the present invention, the systemfurther provides additional data indicating an orientation of theellipse in an atlas or anatomical image space. This is because the sameellipse can be orientated in a number of ways relative to the sameanatomical space. In an example embodiment of the present invention, theorientation information is provided as any two of three angles. Forexample, a first angle can represent an angular offset from thesuperior-inferior line, a second angle can represent an offset from theanterior-posterior line, and a third angle can represent an offset fromthe medial-lateral line. Thus, each of the radii can be a radius drawnalong one of those lines, and each angle can be a respective offset fora respective one of those radii.

Alternatively, geometric primitives other than radii and/or x,y,zcoordinates can be used as an estimate of the volume. For example, ageometric primitive to be used for characterizing a sphere can be adiameter; geometric primitives to be used for characterizing anellipsoid can be axes lengths; geometric primitives to be used forcharacterizing a hexagon can be side lengths; geometric primitives to beused for characterizing a pyramid can be a height, lower radius, upperradius, etc.

Other data can be provided to further define the volumes, e.g., warpingparameters, such as an indication of an amount of warp, a direction ofwarp, etc.

In an example embodiment, a geometric volume can be represented byidentification of elements, voxels, or nodes that are included orexcluded, e.g., the system includes a standard format by which topresent such information.

In an example embodiment of the present invention, a more precise volumecan be saved/transmitted in an Excel, comma-delimited, or other similarformat. For example, in an example embodiment, a volume can berepresented using a first record corresponding to a volume includes aplurality of tuples, each tuple corresponding to a single point in twoor three dimensional space, and a second record identifying each pair ortriple of connected ones of the points. For example, the followingrecord can be stored {x₁,y₁,z₁;x₂,y₂,z₂,x₃,y₃,z₃; . . . }, where eachx,y,z, combination is one point on a perimeter of the volume. Thefollowing additional record can be stored {1,2,3;3,4,5; . . . }, whereeach combination of numbers identifies a respective combination oftuples that are connected. For example, “1,2,3” indicates that the pointof tuple 1 is connected to the point of tuple 2 and to the point oftuple 3. If points of a two-dimensional volume are stored/transmitted,the second record may be in the form of, for example, (1,2;2,3;3,4; . .. ), where each combination of numbers identifies a respectivecombination of tuples that are connected. For example, “1,2” indicatesthat the point of tuple 1 is connected to the point of tuple 2, etc.

Integration of Surgical Planning and Stimulation Programming Systems

FIG. 14 illustrates a paradigm in which surgical planning, stimulationprogramming/planning, and analytics modules are integrated, e.g., bydirect data export from one module to another or by saving ofinformation in a cloud which the information is accessible by all of themodules. For example, the AC/PC/MSP (anterior commissure/posteriorcommissure/median sagittal plane) can be identified in a surgicalplanning system, and can be accessed by the programming module toprogram stimulation settings based on the identified anatomical markers.Similarly, a surgeon can select a target structure or other targetvolume, e.g., manually drawn, as a target for stimulation, which theprogram planning module obtains for use for finding stimulationparameters that are best for providing stimulation of the target region.Similarly an atlas registration can be performed using the surgicalmodule, and the registered atlas can then be used with the programplanning module to accurately select stimulation parameters. In anexample embodiment, for the atlas registration, the surgical planningsystem transmits an identification of a location of a relevant MR, anidentification of a relevant CT, and a number matrix for transformationof the MR and CT information to yield patient atlas.

Pre-op lead location information and a pre-op CT can be provided to thestimulation programming module for use to determine the lead location,on which basis to select stimulation settings for stimulating a targetvolume. MER data of the surgical planning module can also be accessed bythe programming module.

The programming modules can be used for selecting stimulation programs,and generating estimated volumes of activation. Further, the programmingmodule can obtain clinical effects data associated with the VOAscorresponding to the implemented stimulation programs, on which basisanalytics are performed, as described below. The analytics are used torefine target areas, and the information can be provided back to thesurgical planning modules, for view therein by a user. e.g., a surgeon,to better select a target region for future surgeries.

Though not shown in FIG. 13, the surgical planning system of FIG. 14 canhave access to the cloud shown in FIG. 13 to facilitate the describedsystem integration.

FIG. 15 is a further illustration of cloud integration of variousmodules. A system can have any combination of the following components:an implantable stimulator 1502 (including, for example, a IPG and one ormore leads); a remote control (RC) 1504, 1504 a; a clinician programmer(CP) 1506, cloud or other central storage 1508 with a database 1510; anda smartphone 1512 or other computing devices that can accessapplications 1514 (Apps). FIG. 15 illustrates representative flows ofdata, information, and communication between these components includingexamples of the types of information that may flow. It will beunderstood that information flow, although exemplified in one directionin FIG. 15, can often flow in both directions between system elements.

A web-based platform has at least three advantages over a local deviceparadigm. First, fixed hardware platforms inevitably become obsolete ashardware changes occur. Such a scenario would not occur in a web-basedplatform. Second, a web-based platform would enable separation of clientand server and allow deployment of algorithms to which terminals cangain access over time. Third, a web-based platform could dramaticallyaid online analysis.

The modules can include a Patient Data module, a Registration module,and a Patient Programming module. The Patient Data module allows theuser to browse and select patient datasets. The Registration module thenallows the user to select a pre-operative MRI dataset and apost-operative CT dataset. The user then can fuse these datasets andview the fused datasets either individually or in an overlay. Inaddition to fusing MR and CT datasets, the Registration module allowsthe user to automatically or manually determine the positions ofstimulation leads from the post-operative CT images and also enablesemi-automatic registration of the patient's MRI on to a standard Atlas.Once the lead positions are determined and registration is completed,the Patient Programming module allows the user to visualize areas of thebrain activated in response to different DBS stimulation settings. Sincethese areas are depicted in the software in a reference frame thatincludes relevant atlas structures, the user can utilize the display asa guide for optimal choice of stimulation parameters.

These functionalities can be provided in a web-based system, which caninclude the following components: (1) a web-based front end throughwhich the user will control the program, (2) a back-end server whichwill perform a significant portion of the computations required by theuser, and (3) a back-end database to serve as a Laboratory InformationManagement System (LIMS). In an example embodiment, the front-end runsin at least one browser and has a secure connection to the back-endserver.

Front End:

Patient Programming Module:

The Patient Programming Module allows the user to select DBS stimulationsettings and depicts the corresponding VOA. In an example embodiment,the computations for generating the VOA are performed on the client.Alternatively, they are performed on the server with 3D models beingpushed to the client. Either way, the system outputs VOAs and atlasstructures for varying DBS settings. The system rotates Atlas and VOAsthrough (at least) a discrete set of angles to enable appreciation ofintersections between the VOAs and atlas structures and changes of VOAswith varying parameters.

Registration Module:

This module allows scrolling through MR and CT datasets, fusion of MRand CT, auto-detection of leads from CT, and registration of MRI ontoatlas. With respect to the registration, in an example embodiment, theAC-PC (anterior commissure-posterior commissure) is selected and anatlas is selected to match the atlas AP-PC to patient AC-PC. In analternative example embodiment, there is a fully automated registrationalgorithm. e.g., using B-splines. In an alternative example embodiment,the system maintains a large database of patient population MRs, and thesystem finds the best match between the current patient's 3T MR and thedatabase of 7T MRs (or the best few matches).

Patient Data Module:

This module allows users to see which datasets are available on theserver. The user is able to select one pre-operative MR dataset and onepost-operative CT dataset for further analysis. If the LIMS exists,patients can be selected based on their behavioral scores or any othercriteria of choice. Users can also view behavioral measures, such asUPDRS scores as bar plots, and accelerometer readings as timeseries/power spectra.

Back End:

In an example embodiment, the back end has the ability to accept securerequests from the client and display available datasets, providefeedback slices of MR and CT when the user scrubs through the data,perform fusion when user selects one CT and one MR dataset fromavailable list and to feedback fused MR and CT datasets, performregistration and feedback registered MR+CT and atlas structures to theclient, and perform VOA calculation and feed the results back to theclient.

Data Capture on the Remote Control (Patient Programmer)

A need in neuromodulation is to have some way to blind a patient as towhether the patient's device is on or off. This is helpful, for example,for clinical trials. This is difficult because the patient usually has aremote control that informs the patient of this information. Therefore,according to an example embodiment of the present invention, the remotecontrol is provided with a clinical mode, where the remote creates theillusion as though the device is on. e.g., the user can interact with auser interface to raise or lower the stimulation amplitude and/or othersettings, when really nothing is happening in response, although theremote gives the appearance as though the system is responding to theuser's commands.

For example, referring to FIG. 1, a remote control 100 can include adisplay screen 102 including graphical information regarding parametersset in the IPG, including, for example, the pulse width 104, currentamplitude 106, and power amplitude 108 of electrodes of an implantedleadwire controlled by the IPG. The display screen 102 can includeadditional information regarding the IPG, such as one or morerepresentations of its battery power and life 110. The remote control100 can include one or more buttons 112 via which the patient can inputinstructions to the IPG for modifying one or more of the settings. Forexample, the user can, in an example embodiment, select an electrode andinput a desired amplitude setting, polarity. etc. for the selectedelectrode, e.g., by textual input, or by selecting an up or down arrowto raise or lower a setting. In an example embodiment, a graphicalrepresentation of an electric field 109 drawn about one or moregraphical representations of respective electrodes can be shifted, e.g.,using arrow keys, which is interpreted as an instruction to modify oneor more settings to provide the shifted electric field. The remotecontrol 100 can include other features for input of stimulationsettings, for example, as described in the '330, '312, '340, '343, and'314 applications.

In an example embodiment, when the remote control 100 is in the clinicalmode, if the user manipulates the input elements. e.g., buttons 112, ofthe remote control 100 to modify the settings of the IPG, the remotecontrol 100 updates the graphical user interface (GUI) to reflect theinput modifications, without the input modification instruction beingimplemented at the IPG. For example, the remote control 100 can refrainfrom responsively transmitting modification instructions to the IPG, orthe remote control 100 can transmit the instruction, but the IPG canignore the instruction. According to the latter embodiment, the IPGenters the clinical mode, while the remote control 100 is blind towhether the system is in a clinical or a regular mode. Although theinstruction to modify the settings is not executed, the remote control100 can display the modified setting, such as a modified pulse width,current amplitude, and/or power setting, and/or the location(s) of oneor more of the displayed current fields, as though it had beenimplemented.

The remote control 100 can also modify the battery power and liferepresentations 110 to reflect the modifications as though they had beenimplemented. For example, in response to instructions for modificationsthat when implemented would cause a change in the battery power andexpected battery life, the remote control 100 may update the batterypower and life representations to reflect such change, although themodifications are not implemented.

Additionally, in an example embodiment, where the IPG does not performwith the leadwire a stimulation, such that battery power of the IPG isnot being used or is used at a very low rate, but the patient is led tobelieve in clinical mode that a stimulation program is being applied,the remote control 100 modifies the battery power and liferepresentations 10 as though the stimulation program is being applied.

In an example embodiment of the present invention, in the clinical mode,the remote control 100 provides an output. e.g., a graphical, audible,or tactile output, warning of low battery power of the IPG, such that arecharge is suggested, in accordance with the indicated stimulationprogram, although the program is not being applied and the battery poweris in fact not depleted.

In an example embodiment, the remote control 100 includes a charger forcharging the IPG battery. For example, the remote control 100 caninclude a wire with a coil for inductively charging the IPG. In theclinical mode, where the IPG battery is shown to be at less than itsactual charge level, and the user uses the remote control 100 in orderto charge the IPG battery (although the battery might be fully charged),the remote control 100 may update the battery power and liferepresentations 110 to reflect an increase in the battery power andremaining life, as though being increased from the low battery power andlife indications.

In an example embodiment of the present invention, as shown in FIG. 2,the remote control 100 communicates with the IPG 200 and also interactswith a CP (clinician programmer) terminal 202. e.g., a laptop or othercomputer terminal in which a clinician programmer application isexecuted.

For example, a user operating the CP terminal 202 can input upper and/orlower bounds of a parameter of the IPG 200, e.g., upper and loweramplitudes for a stimulation program. The CP terminal 202 can transmit.e.g., wirelessly, data to the IPG 200 for setting the upper and/or lowerbounds within the IPG 200. The patient can operate the remote control100 to set one or more stimulation parameters of the IPG 200. However,the IPG 200 ignores parameter settings received from the remote control100 that are not within the upper and/or lower bounds set by the CPterminal 202. Alternatively or additionally, in an example embodiment,when the remote control 100 communicates with the IPG 200, the IPG 200responsively notifies the remote control 100 of the restrictions set bythe CP terminal 202, and the remote control 100 thereafter refrains fromtransmitting to the IPG 200 settings that do not comply with therestrictions, until the IPG 200 informs the remote control 100 ofremoval or modification of the restrictions.

In an alternative example embodiment, as shown in FIG. 3, the CPterminal 202 communicates restrictions concerning the stimulationsettings to the remote control 100, and the remote control 100 refrainsfrom transmitting instructions to the IPG 200 that do not satisfy thoserestrictions. For example, if the user inputs an instruction to set astimulation amplitude to a level that is higher than an upper boundcommunicated by the CP terminal 202 to the remote control 100, theremote control 100 ignores the user input instruction, e.g., at leastwith respect to responsively transmitting an instruction to the IPG 200.

In an example embodiment, such bounds may be set in a clinical mode,such that the remote control 100 responds to a user input to modify aparameter to a level that is beyond that which is allowed by theinstructions of the CP terminal 202 by accordingly modifying the GUI inthe display screen 102, but refrains from sending instructions to theIPG 200 to set a parameter to the impermissible level, or, according tothe embodiment described with respect to FIG. 2, the remote control 100possibly sends the instructions, which the IPG 200 ignores according tothe restrictions received from the CP terminal 202. However, as notedabove, in an example embodiment, the IPG 200 can also communicate to theremote control 100 the restrictions set by the CP terminal 200.Additionally, in an example embodiment, the IPG 200 informs the remotecontrol 100 that it is operating in clinical mode, and the remotecontrol 100 responsively modifies its output as described above toprovide the illusion of changes being implemented even though they arenot being implemented.

The embodiment described with respect to FIG. 2 may be preferable overthe embodiment described with respect to FIG. 3 so that if a new remotecontrol is used, the CP terminal 202 need not resend the restrictions tothe new remote control.

In an example embodiment, a clinician can put the device in a mode suchthat it goes on and off at various preset times, and the patient doesnot know when it is on or off. For example, the CP terminal 202 can sendinstructions concerning such a stimulation program to the IPG 200, whichcan, in turn, inform the remote control 100 of the stimulation program.e.g., which cannot be overridden by the patient via the remote control100, or which can be overridden by the patient in only defined limitedways, e.g., for safety reasons. Meanwhile, the remote is configured toreceive from the patient input indicating how the patient is doing. Suchfeedback may include input of a number on a predetermined scale. Forexample, the device outputs a reminder to input the information. So nowclinical trial data can be obtained where information on how the patientis doing is periodically received, and the patient does not know whenthe device is on or off. Patient feedback may be time-stamped forsubsequent clinical analysis.

Additionally, in an example embodiment, the device changes the programused to stimulate at various intervals, and the remote does not indicateto the patient which stimulation parameters are being used at that time.The patient then records over time how the patient is doing. Over time,the device learns which program is best for the patient by determiningfor which parameters the patient has been indicating the patient feelsbest. For example, the device can iterate through a number of settingsfor each electrode, gradually increasing the amplitude at a respectiveelectrode contact of the leadwire, and continuously do so as long as thepatient provides good feedback about that setting. In this exampleembodiment, the patient does have the ability to manually override thepredetermined settings, for example, in case the device automaticallysets a dangerous setting. Therefore, recorded feedback may includepatient override requests.

In an example embodiment, there can be sensors that sense how thepatient is doing. In addition to the patient manually entering how thepatient is doing, the sensor information can be used to indicate how thepatient is doing. Such sensors may include, for example accelerometersor other sensors that detect motor skill and/or cognitive functioning,for example, tremor (motor skill), dwell times (motor skill/cognitive),etc. The sensors may be integrated into the remote, the IPG or any otherhardware that the patient carries.

The information on how the patient is doing and the related stimulationparameters can be stored at the central server.

In an example embodiment of the present invention, the presetstimulation program, whether including a single steady set of parametersettings, or including a plurality of sets of parameter settings thatare implemented at different times, e.g., at different intervals, can beset in a clinical mode, as described above, where the GUI of the remotecontrol 100 is modified to reflect changes entered by the patient,although such changes are not implemented. In an example embodiment,even in a clinical mode, the system may allow the user to overridecertain settings for safety reasons.

According to an example embodiment of the present invention, the systemmay be configured to perform a clinical study for testing varioussettings, including, for example, testing a response to an on-lowsetting at which a low power stimulation is applied, an on-high settingat which a high power stimulation is applied, and an off setting atwhich no stimulation is applied. In an example embodiment the clinicalstimulation program includes cycling through the three (or more)settings one or more times at equal or varying intervals. As explainedabove, the patient can be blind to the changes, and the system can beconfigured to record information regarding the patient's condition atvarious points during the stimulation program, which information can beobtained from user input and/or from sensors.

In an example embodiment of the present invention, the system mayinclude an electronic diary (“e-diary”) feature for recording a log oftime-stamped patient condition information, and for recordingtime-stamped information concerning the stimulation settings, so thatthe patient condition information can be associated with particularstimulation settings. Certain of the recorded information can pertain tofactors that are not a result of the stimulation settings. e.g., whichmedication(s), if any, the patient is taking. Other of the patientcondition information can be associated with a combination of thestimulation settings and the medication(s) the patient was taking at thetime associated with the patient condition information.

In an example embodiment of the present invention, for obtaining patientcondition information, medication information, etc., the remote control100 includes user input hardware and/or software controls via which thepatient can enter information. In an example embodiment, the remotecontrol is configured to receive input from the patient of entry of anumber on some number scale, e.g., 1-10, of how the patient is feeling.In an example embodiment of the present invention, the remote control100 includes a “good” button and/or a “had” button by which the patientcan generally indicate whether the patient generally feels good and/orbad. In an example embodiment of the present invention, the remote 100includes soft and/or hard buttons (or check boxes, radio buttons, etc.)for predetermined significant events, such as, for example, falls,seizures, etc., which the patient can select when such an event occurs.The system can record a time-stamped entry in the e-diary noting theoccurrence of the event indicated by the selection of the correspondingevent input.

In an example embodiment, the remote control 100 stores the e-diaryinformation locally in a long-term storage of a memory device of theremote control 100. In an example embodiment, the remote control 100alternatively or additionally transmits the e-diary information to theIPG for storage therein. In an example embodiment of the presentinvention, the c-diary information is alternatively or additionallyuploaded to a central server. e.g., as discussed above under the “CloudData Management” section.

As noted above, in an example embodiment the system is configured torecord a time-stamped log of the stimulation settings. In an exampleembodiment, the IPG records time-stamped stimulation settings atpredetermined intervals. In an alternative example embodiment, the IPGrecords time-stamped stimulation settings responsive to a change to thestimulation settings. In an example embodiment, after recording initialsettings, subsequent settings are recorded as a change to theimmediately preceding settings.

In an example embodiment of the present invention, the system correlatesrespective portions of the patient-condition information to respectivesettings based on the time-stamps, and automatically modifies settingsbased on the correlation. For example, in an example embodiment, thesystem detects a trend, e.g., that with increase of a certain parameterbetween a first time and second time, the patient condition hasdeteriorated, and therefore modifies the settings. e.g., in a reversedirection in response to a detected deteriorated condition and/orfurther in a same direction in response to a detected improvement incondition.

In an alternative example embodiment, or additionally, the systemoutputs a report of the effects of the settings on the patientcondition. For example, in an example embodiment, the system outputs areport that an increase or decrease of parameter ‘x’ has been detectedto be associated with a deterioration or improvement of condition ‘y’.

In an alternative example embodiment, or additionally, the systemoutputs a timeline covering a time period including some or all of thetime-stamped times and further outputs against the timeline (a) a graphrepresenting changes to one or more patient conditions indicated by thepatient-condition information, and (b) identifications of the settingsprevailing at different times of the timeline.

VOA Selection for Target Volume

A target volume can be selected, e.g., by a user or by the system, e.g.,based on clinician input, the patient's information (such as a patientdisorder, patient history, etc.) population information (such as learnedinformation from one or more other patients), therapeutic goal, etc. Inan example embodiment of the present invention, the system outputssuggested stimulation settings and/or outputs a graphical VOAcorresponding to suggested stimulation settings for such a targetvolume.

Referring to FIG. 4, at step 400 the system obtains a target volume. Atstep 402, the system determines a plurality of sets of stimulationsettings that provide VOAs considered similar to the target volume. Thesystem can perform such a determination according to a predetermined oneor more conditions, such as a degree to which a VOA must overlap thetarget volume and/or a maximum amount by which the VOA can spill beyondthe boundaries of the target volume. In at least some embodiments, theconditions can be selected and values chosen by the clinician or otheruser. At step 404, the system sets the IPG of one or more patients,e.g., for whom the target volume (or a similar target volume) isobtained, to test some, or each, of the plurality of sets of stimulationsettings. The settings may be tested on a single patient. e.g., theparticular patient for whom the system will output the suggested optimalsettings in view of the obtained target volume, or across a patientpopulation. According to an example embodiment, where the settings aretested across a patient population, different ones of the sets ofstimulation settings can be tested in parallel. According to an exampleembodiment, where the settings are tested by applying the sets ofstimulation settings to a single patient, the system cycles through aprogram in which different sets of the stimulation settings are appliedin a sequence over time, different ones of the sets being applied duringdifferent intervals of the program.

At step 406, the system obtains patient condition information for thetested settings. Steps 404 and 406 may be performed concurrently. Thatis, while a patient is stimulated by a set of stimulation settings, thesystem is configured to obtain information concerning the patient'scondition. e.g., via patient input or by sensor signals, as describedabove. The information and settings can be time-stamped. The conditioncan include therapeutic effects, side effects, patient ratings, and thelike, or any combination thereof.

In an example embodiment, for each of the patients on which the sets ofstimulation settings are tested, the system associates the patientcondition information with the set of stimulation settings applied tothe respective patient for whom the respective patient conditioninformation was obtained, the association being based on a determinedcorrespondence of the timestamps of the patient condition informationand the applied set of stimulation settings, as explained above.

In an example embodiment, at step 408, the system assigns a score toeach of the sets of stimulation settings based on the patient conditioninformation associated with the respective set. For example, differentweights can be applied to different types of patient conditioninformation to calculate an overall score. According to an embodiment inwhich the sets of stimulation settings are tested across a patientpopulation, the system can test a same one of the sets on multiplepatients. In an example embodiment, the system calculates an averagescore of the scores calculated for each patient for whom the set ofstimulation setting was applied.

At step 410, the system may compare the calculated scores and select apredetermined number or percentage of the best scoring, e.g., the 3highest scoring or the single highest scoring, tested set(s) ofparameter settings as candidate parameter settings (and associated VOAs)to output as suggestions for a patient for whom the same or similartarget volume is selected.

The target volume selection and/or the selection of suggested settingscan be performed on any computing device, e.g., a CP terminal.

In an example embodiment of the present invention, the sets of settingscan be tested in a clinical mode during which the patient is blinded tothe settings.

Programming Based on IPG Efficiency

It is possible for a plurality of different sets of stimulation settingsto result in the same or similar VOAs, where certain ones of the sets ofstimulation settings are more electrically efficient than others of thesets. For example, similar tissue activations may be obtained by varyingthe electrical amplitude and pulse width. For example, first settingshave a high amplitude and a short pulse width can be equivalent orapproximately equivalent to second settings having a lower amplitude buta longer pulse width. For example, equivalence can be measured in termsof power or total current delivered or by any other relevant measure,including the strength/duration curve discussed below, and“approximately equivalent” can be, for example, a variation of 1, 2, 5,or 10 percent.

In an example embodiment of the present invention, the system can instep 402 select a plurality of electrically equivalent settings thatdiffer in their respective amplitudes and pulse widths. It is noted thatalthough such sets of settings may be considered electrically equivalentand/or calculated to produce equivalent or substantially equivalentVOAs, it may nevertheless occur that the different sets of settingsproduce different clinical effects. Therefore, in an example embodiment,the system tests these equivalent sets at steps 404 et seq.

In an example embodiment of the present invention, the system alsoassigns a weight to electrical efficiency for the calculation of thescores at step 408.

In an example embodiment of the present invention, the system finds aplurality of sets of electrically equivalent stimulation settings usinga strength/duration curve. For example, in an example embodiment, atstep 402, the system determines a set of stimulation settings that isestimated to produce a VOA that best fits the target volume, and thenfinds other sets of stimulation settings that are electricallyequivalent to the determined set of settings based on thestrength/duration curve.

According to an example embodiment of the present invention, the systemuses a strength/duration curve that relates to the discharge of an IPG.In an example embodiment, a device is programmed. e.g., automatically,to use the least amount of energy to fill the target volumes based onthe strength/duration curve. In an example embodiment, the efficiency ofthe settings is one of a plurality of factors contributing to a score onwhose basis a set of settings is selected, as described above, where,all else being equal, greater efficiency results in a higher score.

In this regard, according to an example embodiment, programming settingsare automatically adjusted towards a target volume specified by a user(or otherwise selected). The visualization system is configured to,based on the specified target volume, test settings that use the lowestpower consumption while reaching the specified target volume. In anexample embodiment, the system also tests settings that yield volumesthat approximate the target volume (e.g., slightly larger or smallerthan the target volume). Additionally, in an example embodiment, thetesting of such settings can be performed during the clinical mode, sothat the optimal settings (in terms of a combination of therapeuticeffectiveness and power consumption) is obtainable with the aid offeedback from a blinded user.

FIG. 5 shows an example strength/duration curve, where the ordinaterepresents the amplitude and the abscissa represents the pulse width,where the plotted points are all estimated to produce substantiallyequivalent volumes of activation. The graph shows that the higher theamplitude, the shorter the required pulse width for producingsubstantially the same volume of activation. That is, a fiber isexpected to fire based on a combination of amplitude and duration of thestimulation at that amplitude, so that the higher the amplitude, theshorter the required duration for causing the fiber to fire.

According to an example embodiment of the present invention, for aselected VOA, the system plots the strength/duration curve of valuesthat are estimated to produce the selected VOA, and selects the mostefficient of the pairs of values, e.g., assuming all other factors beingequal (as noted above, other factors may result in selection of a set ofvalues different than those of the most efficient pair).

For example, the system can obtain a target volume. e.g., user-selectedor automatically selected. The system then determines one or moreclosely matching producible VOAs. The system is configured to select,for each of one or more of such VOAs, a most energy efficient pair ofamplitude and pulse width values to produce the respective VOA. Forexample, where a remaining battery power is 3.7 v and a requiredamplitude is more than 3.6 volts, the system can use capacitors todouble the voltage to 7.4 v. If less than 7.4 v is required, the systemcan burn off the difference between 7.4 v and the required voltage. Forexample, if 4 v is required, the system can burn off 3.4 v, which isinefficient. Accordingly, for the 4 v requirement, the system candetermine from the strength/duration curve whether there is a moreefficient pair of settings. For example, the system might determine thatthe same VOA is producible with a longer pulse width at 3.5 v.

SFM Analytics

Example embodiments of the present invention pertain to determining atarget volume by analysis of VOAs for a plurality of patients.

According to an example embodiment of the present invention, a systemcan include program code for providing visualization features to outputgraphical representations of estimated VOAs. e.g., about arepresentation or image of an implanted leadwire and/or overlaying amodel or image of a patient anatomy. The system can include code bywhich user, e.g., clinicians or patients, can test various settingsestimated to produce such VOAs. The system can also include analyticscode for determining a target volume, e.g., based on such VOAs tested bythe users.

In an example embodiment of the present invention, the system includesfeatures for facilitating the sharing by users of target volumes thedifferent users have selected. In an example embodiment, the systemincludes features by which users can share data, such shared data beingsubjected by the system to analytics to determine optimal target volumesand/or optimal stimulation settings and corresponding VOAs.

Systems Configurations:

In an example embodiment of the present invention, the SFM analyticsfeatures are provided as part of a stand alone visualization system. Forexample, A Guide system can be used to modify/test parameter settingscorresponding to VOAs and/or side effect volumes (volumes wherestimulation is preferably avoided), and/or to set target volumes, whichVOAs, side effect volumes, and/or target volumes can be transported to aseparate analytics system on which analyses can be run. In analternative example embodiment of the present invention, the SFManalytics features are provided in a Guide system including theclinician programmer features by which to program the settings of theIPG, such that the analytics by which to find optimal settings isconveniently on a system used to actually program the implanted device.

According to an example embodiment of the present invention, analyticsinformation and input for performing analytics can be stored remotelyvia a cloud/internet-based system. In an example embodiment, the datafrom many systems, e.g., workstations operated by many users, can bestored centrally, and the centrally stored data and/or the resultinganalytics information can be accessed by a plurality of users ofnetworked systems.

In an example embodiment, the analytics features are provided in asoftware package that users can load onto the users' computers.Alternatively, the analytics features can be provided as a web-basedapplication.

In an example embodiment of the present invention, the system isconfigured to allow a user to limit access to the data associated withthe user, e.g., data created by the user or about the user, to onlycertain users (e.g., only one or more certain specified users or onlyusers of one or more certain specified user groups) or to only certainsystems (e.g., only via the Guide system). For example, the system canrequire entry of a user ID by which the system determines whether a useris authorized to access such restricted data.

It is noted that the analytics software and the input and/or output datacan be at different locations.

Analyses of the SFM Analytics:

1. Population Overlap:

According to an example embodiment of the present invention, the SFManalytics system obtains as input a group of VOAs from a population ofpatients, where each VOA is associated with a measure of effectiveness,and the SFM analytics system determines a target volume based on theinput information. For example, a collection of VOAs can form a group tobe subjected to the analytics calculations where there is a clinicallysignificant commonality between the VOAs of the collection. For example,VOAs of patients who share a certain diagnosis. e.g., the patients allhave Alzheimer's disease, can form a clinically significant group foranalysis to determine a target volume for treating Alzheimer's disease.Another or alternative significant commonality can be that the VOAs areassociated with similar anatomical locations at which the stimulationelectrode is implanted.

According to an example embodiment, the system is configured for a user,e.g., a physician, to manually create a group of VOAs to be used asinput to analytics functions. For example, a physician might notice thata number of VOAs of stimulation settings applied to one or more patientsprovided excellent results, and the user can form a group for such VOAs.A single VOA can be a part of multiple groups.

In an example embodiment, for the analysis of a group of VOAs, thesystem places all of the VOAs in a common spatial reference space. Forexample, the system is configured to transform one or more, e.g., all,of the VOAs into a common atlas space. This may be required for examplewhere the VOAs were obtained for different patients whose anatomicalmakeup varies.

The system is configured to determine where the VOAs of the commonreference space spatially overlap for determining a target volume. Forexample, the system can output a combination of a collection of points.e.g., voxels, that belong to all or a threshold number or percentage ofthe VOAs of the group as a target volume. In this regard, VOAs eachencompass a collection of points, e.g., voxels. According to an exampleembodiment, the system provides a user interface configured for userinteraction therewith to input the threshold number or percentage.

Alternatively, the system can perform more complex calculations forfinding voxels of significance shared by some of the group of VOAs, thecombination of voxels of interest forming a target volume.

For example, in an example embodiment, the system is configured forobtaining ratings for each of the group of VOAs. e.g., one or moreratings for some characteristic, e.g., therapeutic effect, side effect,or how well it helped the patient with respect to some score. Forexample, clinicians can input into the system a rating on how well thepatient is doing against some standardized scale.

The system is configured to assign a greater weight to those VOAsassociated with better scores. e.g., the greater the score, the greaterthe weight. For example, the system can weight each point, e.g., voxel,within a VOA by the VOA's score. Then the system calculates for each ofthe points within any one of the group of VOAs, a respective score basedon the combined weighted scores of the point across all VOAs of thegroup that include the respective point. For example, the system can sumthe scores for each of the points. Alternatively, the system can averagethe scores for each of the points. According to the latter embodiment,the system also takes into consideration the number of VOAs in which thepoint is included. For example, a score of 0, a negative score, or someother value can be assigned to a point for a VOA in which it does notappear. Alternatively, the number of VOAs of the group in which thepoint is included can be considered as a separate factor in thecalculation. According to an example embodiment of the presentinvention, the system compares each point's value to a threshold, andincludes a point as part of an output target volume if the point's scoremeets the threshold. According to an example embodiment, the systemprovides a user interface configured for user interaction therewith toinput the threshold score. According to an example embodiment of thepresent invention, the system selects a threshold number or percentageof highest scoring points as the target volume. According to an exampleembodiment, the system provides a user interface configured for userinteraction therewith to input the threshold number or percentage.

According to an alternative example embodiment of the present invention,the above described thresholding can be performed to produce a volumewhich the system can subject to further calculations from which toselect a target volume for output.

2. Group Comparisons:

In an example embodiment of the present invention, the system isconfigured to compare different groups of VOAs to determine targetvolumes of stimulation and/or volumes to be avoided. e.g., so as not toproduce an unwanted side-effect. VOAs can be associated with respectivetherapeutic effects and/or side effects, including by degree ofseverity. For example, such associations can be based on user inputprovided using user interfaces such as those described for example nU.S. patent application Ser. No. 14/212,730, filed Mar. 14, 2014 andU.S. Prov. Pat. App. Ser. Nos. 61/793,773 filed Mar. 15, 2013 and61/830,855 filed Jun. 4, 2013, the entire content of each of which ishereby incorporated by reference herein. Effects, associated with theVOAs, can also be obtained based on sensor information obtained duringstimulation or in a period immediately following the stimulation. In anexample embodiment, the associated effects are used for obtainingrelevant volumes on which basis to generate new target volumes and/orside effect volumes.

For example, a first collection of VOAs associated with a certain sideeffect can form a first VOA group and a second collection of VOAs notassociated with the side effect can form a second group. The system canautomatically create these groups. Alternatively, a user can manuallyform the groups and input an instruction to the processor to perform acomparison. Similarly, the system and/or the user can select certaintherapeutic effects as the characteristic by which to group VOAs. Forexample, an improvement in motor skill or a motor skill score can be setas a therapeutic effect by which to group VOAs.

The system is configured to transform the VOAs to a single common atlasspace and find an area included in the group associated with the sideeffect (or therapeutic effect) and not included in the group that is notassociated with the side effect (or therapeutic effect), and output thearea, e.g., in relation to an atlas space, as an area that should not bestimulated. According to an example embodiment, more than one sideeffect and/or more than one therapeutic effect can be combined for thegroupings, e.g., as a logical OR (e.g., any VOA associated with any oneor more of certain specified side effects or therapeutic effects) or asa logical AND (e.g., any VOA associated with the combination ofspecified side effects or therapeutic effects). According to an exampleembodiment, the system is configured for use of a combination of sideeffect and therapeutic effect information for grouping VOAs in analyticsfor selecting a target VOA, by combining therapeutic effect areas andsubtracting therefrom the side effect areas. According to an exampleembodiment of the present invention, the system provides a userinterface configured for user interaction therewith to input a thresholddegree of the side effect and/or therapeutic effect required forconsideration of the respective VOA as part of the group.

Alternatively, a more complex calculation can be used to determine thepoints of the area to be avoided. For example, each point can beindividually scored based on a combination of scores of all VOAs of thegroup associated with the side effect and in which the respective pointis included. e.g., where the score for a point within a VOA depends onthe severity of the side effect for that VOA. In an example variant ofthis embodiment, the system first finds which areas are included in athreshold number and/or threshold percentage (e.g., 100%) of the VOAsassociated with the side effect and not included in a threshold numberand/or percentage (e.g., 100%) of the VOAs not associated with the sideeffect. For voxels in the identified area, the system assigns respectivescores based on the severity of the side effect for the VOAs in whichthe voxel is included. Alternatively, for each voxel, the system assignsa score based on a combination of those VOAs associated with the sideeffect an in which the voxel is included and of those VOAs notassociated with the side effect. For example, inclusion in a VOAassociated with the side effect can contribute to a higher side effectscore, the extent by which the score is raised being dependent on thequantified severity of the side effect with which the VOA is associated;and inclusion in a VOA not associated with the side effect cancontribute to a lowering of the score of the voxel. The system includesthose points whose combined score meets a predetermined threshold, or athreshold number or percentage of points sorted by score, as the volumeto be avoided.

Similarly, in an example embodiment of the present invention, where abenefit is associated with a first group of VOAs and is not associatedwith a second group of VOAs, the system finds the points. e.g., voxels,that are included in the VOAs of the group associated with the benefitand not included in the group that is not associated with the benefit,or scores points by the extent of their inclusion in one group over theother group, as described above, to output the combination of suchpoints as a target volume.

According to an example embodiment, the system can, based on the VOAs ofthe patient population and their corresponding clinical effects,determine on a voxel-by-voxel basis, which voxels contribute to acertain effect, and combine those voxels into a target or side-effectvolume. For example, if a voxel is included equally in both VOAsassociated with a particular clinical effect and VOAs not associatedwith that clinical effect, then the voxel can be considered not tostatistically significantly contribute to the particular effect. On theother hand, if a voxel is included statistically significantly more inVOAs associated with the effect than those not associated with theeffect, then the voxel can be treated as being one that helps contributeto the specified effect when stimulated.

According to an example embodiment, the patient population VOAs andtheir effects can be used to construct electric field maps on avoxel-by-voxel basis with corresponding scores, for example, asdescribed in U.S. patent application Ser. No. 13/600,855 filed Aug. 31,2012, which is incorporated herein by reference in its entirety, toobtain a value for each voxel with respect to the specified effect.

According to an example embodiment, the system is configured to generatea probability voxel map that maps the probability that stimulation ofeach respective voxel will contribute to the specified effect, thesystem then selects all voxels whose probabilities meet a predeterminedor user-input threshold probability, and the system then draws athree-dimensional surface outline around all the voxels meeting thethreshold which are at the extremities to form the target or side effectvolume. In an example embodiment, with further information concerningthe leadwire location, the system is configured to output thestimulation parameters for stimulating the thus generated target regionor for avoiding the thus generated side effect region.

In an example embodiment, a physician inputs desired therapeutic effectsvs. side effects. Those therapeutic effects and side effects areweighted and overlaid/summed. A 3D voxel map is generated. A leadtrajectory is placed in this space. Possible VOAs based on that leadtrajectory are predicted and scored. The best score, weighted againstneeded settings, is chosen, and final settings proposed. For example,for each VOA/contour, map to a field, then inverse from field toprogrammed amplitude/pulse width settings. To choose a VOA, use sphereon radius r, placed along lead at spacing dx, and choose location x forsphere with maximal score.

3. VOA Steering Based on Clinical Effects/Indications/SFM Analysis:

According to an example embodiment of the present invention, the systemprovides a user interface for input of desired therapeutic effectsand/or undesired adverse side effects to be considered. e.g., in theform of a questionnaire. Once the questionnaire is completed andsubmitted. e.g., by the press of a “submit” button, the system outputs asuggested set of stimulation parameters corresponding to a VOA and/oroutput the suggested VOA. For example, the system analyzes prior VOAs,e.g., as explained above, to determine the regions associated by thecorrect VOA corresponding to the indicated effects. According to anexample embodiment, the system also provides for alternatively receivinginput of indications of a patient, and the system finds the VOAs of thepatient population corresponding to stimulations performed for otherpatients with the indicated indication(s), and outputs the overlapping(or other combination) VOA regions. According to an example embodiment,the system is configured to receive as input a set of indication(s) andclinical effect(s), and use the combination to filter the VOAs fordetermining and outputting a target volume.

According to an example embodiment, the system includes an input devicesuch as a dial, as a hardware component or as a soft input devicedisplayed as a user-interactive graphical component in a user interface,by which the user can input a change in a desired clinical effect orinput a degree to which to consider an adverse effect to be avoided. Forexample, the user can turn a dial that is associated with tremor toindicate the degree to which the recommendation of a target stimulationlocation should be based on obtaining the desired therapeutic effect ofreducing tremor.

In response to user interaction with the input device, e.g., in responseto the user turning the dial, the system outputs the next closestprogram to result in that input change. The change in program for thedesired change in clinical effect can be with respect to location ofstimulation, pulse width, frequency, amplitude, etc.

An adjustment in some parameters to obtain a greater degree of theindicated therapeutic effect can result in an increase of adverseeffects. Thus, in an example embodiment, the system determines thenearest VOA to result in the increased indicated therapeutic effectwithout the increase in the adverse side effect, or, where no such VOAexists, the one with the least increase in adverse side effect.Accordingly, in an example embodiment, the system finds the VOA closestto the VOA associated with the current settings that is also associatedwith the desired effect and not associated with the adverse effect. Thesystem then outputs the program settings associated with the VOA closestto the VOA associated with the presently indicated stimulation settings,or, according to an alternative example embodiment, the VOA associatedwith the settings most similar to the presently indicated settings,where the modified settings produce the indicated desired change inclinical effect.

According to an alternative embodiment, the system determines the VOAfor producing the greatest amount of the indicated desired change,determines a trajectory of possible VOAs between the one correspondingto the presently indicated settings, and, as the user turns the dial,the system outputs those VOAs and/or corresponding stimulationparameters, in succession until the optimal VOA is reached. According toan example embodiment, the system is configured to output a visual ofthe VOA path from the current location to the optimal location. Forexample, the system simultaneously outputs the current and optimal VOAs,as well as those in between, each for example being demarcated by arespective outline. In an example embodiment, as the user turns thedial, a different one of the displayed VOAs in the path is highlighted,and its associated parameters displayed.

Thus, for example, a presently set stimulation program is defined(partially) by amplitude, pulse width, rate, and location of stimulationpulses. A control, such as a dial, is provided for a correspondingeffect or symptom. For example, a dial can be provided for tremorcontrol. As the user turns the dial, the system auto-adjusts theparameters, e.g., auto-adjusts the amplitude setting, to graduallyevolve the VOA corresponding to the current settings to the VOAassociated with optimal tremor control, with each incremental turn ofthe dial moving the VOA another step along a tremor improvement paththat extends from the current VOA location to that corresponding to theoptimal tremor control.

FIG. 11 shows an example current VOA 1100, an Optimal VOA 1102 forimprovement with respect to tremor, and a tremor improvement path 1104outlining a trajectory from the current VOA 1100 to the Optimal VOA1102.

Intermediate locations along the path can be associated with adverseside effects. According to an example embodiment, the system isconfigured to output warnings when intermediate VOAs are associated withcausing adverse side effects. In an example embodiment, if multipletrajectories can lead from the current VOA to the optimal VOA, fortremor control for example, the system is configured to select thetrajectory that avoids VOAs associated with adverse side effects, orthat entails fewest VOAs associated with adverse side effects (eventhough the trajectory is not the shortest of the trajectories).According to an alternative example embodiment, the system is configuredto skip over VOAs associated with any adverse side effects, oralternatively VOAs associated with severe side effects.

According to an example embodiment, the system is configured toalternatively or additionally perform the reverse, where the user inputsa stimulation program, and the system determines, based on the VOAs ofthe patient population and their corresponding indicated clinicaleffects, the expected therapeutic and/or adverse side effects of theindicated program. The system then outputs the expected clinicaleffects.

According to an example embodiment, in addition to outputting theexpected clinical effect, the system is also configured to determine andoutput expected effects with certain slight modifications to thestimulation parameters. For example, in an example embodiment, thesystem outputs a message stating that if the stimulation is shifted abit higher or rotationally around the leadwire by a certain number ofdegrees in a particular rotational direction, etc., then a particularspecified change in clinical effect would be obtained. In an exampleembodiment, the system limits such output to minor changes. e.g.,movement of the stimulation up to a certain distance upward or downward,or a certain number of degrees around the leadwire, or a certainthreshold additional or lesser distance radially outward from theleadwire, etc. Alternatively, the system outputs the next expectedchange in effect for each of one or more of such changes regardless ofthe extent of the change. e.g., the next change in effect expected witha shift of stimulation upward regardless of the amount of such upwardshift. The system or user may define the size of the minor change andmay be, for example, a change of 1, 2, 5, 10 percent or more in thestimulation parameter.

According to an example embodiment of the present invention, a user canuse a user interface of the system to steer stimulation, for example asdescribed in U.S. patent application Ser. No. 14/011,836 filed Aug. 28,2013 and/or in U.S. Prov. Pat. App. Ser. Nos. 61/693,866 filed Aug. 28,2012, 61/699,135 filed Sep. 10, 2012, 61/699,115 filed Sep. 10, 2012,and 61/753,232 filed Jan. 16, 2013, the contents of all of which arehereby incorporated by reference herein in their entireties. In anexample embodiment, as the user shifts the stimulation, the systemchecks the patient population VOAs to determine whether the steeredchange shifts the VOA estimated for the new steered settings towards alocation associated with an adverse effect, in which case the systemoutputs a warning signal. e.g., visually, haptically, and/or aurally.For example, according to an example embodiment, a signal is graduallyincreased as the VOA is steered closer to, or to cover more of, the areato be avoided.

4. Group Analysis Considering Biological Networks:

The body includes various biological circuitries that biologicallyrelate various parts of the body to each other in various respectiveways. For example, as described in U.S. Prov. Pat. App. Ser. No.61/904,248 filed Nov. 14, 2013, the entire contents of which is herebyincorporated by reference herein in its entirety, stimulation of oneanatomical region can cause an effect in another anatomical region.Thus, according to an example embodiment, where there are VOAs grouped,for example by similar therapeutic or side effect regions, the system isconfigured to, for one or more particular biological circuitries,determine an overlap (if any) by a significant number of the VOAs with ashared component of the considered biological circuitry for generationof a target or side effect biological component with respect tostimulation. For example, in an example embodiment, the system isconfigured to determine whether a threshold number or percentage of VOAsthat are associated with a particular therapeutic effect or side effectoverlap a shared neurological fiber (even if the VOAs are innon-overlapping anatomical regions), and if so output an indication ofthat biological fiber as a target fiber or a fiber to be avoided(depending on whether it is associated with a therapeutic effect oradverse side effect). In fact, all of the features described herein withrespect to determination and output of target or side effect volumes canalso be used for determining and outputting target or side effectbiological structures such as neurological fibers (for example, insteadof returning a target volume in response to the input indications and/orclinical effects to be considered, the system can return a target of oneor more fibers).

According to an example embodiment, the system uses a combination ofregion overlap and biological circuitry overlap for generation of atarget volume or side effect volume. For example, the system generatesthe volume based on anatomical region overlap of the volumes, but onlythose volumes which overlie a shared biological component of aconsidered biological circuitry are grouped into a new target or sideeffect volume. For example, if neurological fibers are considered, thenthe VOAs associated with a same, for example, therapeutic effect arecombined to form a new target volume conditional upon that they bothoverlie the same neurological fiber (of the respective patients withwhich they are associated).

According to an example embodiment of the present invention, the systemdisplays putative functional subdivisions of a relevant anatomicalregion, e.g., the STN, and the putative connections between theanatomical region, e.g., the STN, and other regions, e.g., the pallidum,pallidum and thalamus, thalamus and cortex etc. When a VOA is activatinga particular part of the STN, the system lights up corresponding nodesalong the circuit and pathways within the biological circuit. In anexample embodiment of the present invention, the system provides thedisplay in a user interface in which a user can click the pathways, inresponse to which the system displays links to literature discussing therelevant biological connections. In an example embodiment, the systemprovides this information in a wiki in which the plurality of users ofthe system can provide additional source and explanatory informationconcerning the biological connections.

In an example embodiment of biological network/circuit analytics, fiberscan be stimulated at different locations along some fiber(s). Systemknows that two points or structures are in some biological circuit ordifferent points along the same fiber tract, and thus related and mayhave the same primary effect (perhaps with different secondary effects).For example, when planning an implantation and stimulation target, ifthe clinician desires to stimulate target A, but it is not possible (forexample, other structures are in the way of target A), a target C thatproduces the same primary effect can be used and, therefore, implant intarget C.

As another example, after implantation, the clinician desires tostimulate target A, but cannot because the lead is not in the necessarylocation, a target C that produces the same primary effect can be usedand, therefore, program stimulation towards C. In these examples, theanalytics determine that targets A and C have been shown to produce thesame (or similar) effect, although they are spatially non-overlapping.Target volumes often reduce to a point but with, for example, DTI data,target volumes can reduce to a line.

5. Group Analysis Considering Biological Signals:

There are many types of brain signals corresponding to respective brainstates, including for example, electrophysiological brain states.Examples of such signals include MER and Local Field Potential (LFP).Such signals can be location specific, e.g., to particular parts of thebrain. Similarly, components in medical images can correspond torespective brain states, and therefore medical images, such as, forexample, fMRI, PET and SPECT, also correspond to respective brainstates. Such brain state data can be obtained and associated withpatients and their respective VOAs. For example, the brain can bestimulated while also obtaining signals, such as MER, PET. EEG, and/orneuro-activation spikes. According to an example embodiment the systemis configured to use such signals as a signature with which the VOAs areassociated, for the purpose of VOA groupings, similar to that which isdescribed above with respect to using the same therapeutic effect(s)and/or side effect(s). A single brain state can be represented by acombination of signal types. Where a number of VOAs are associated witha selected signal signature, the system is configured to generate avolume by the intersection (or union) of those volumes. For example, thesystem can generate a plurality of volumes each associated with adifferent respective MER signal signature. If there is a desired brainstate for a patient, the user can enter the relevant brain state, e.g.,MER signature, in response to which the system outputs a volume that isbased on the VOAs associated with the indicated signal signature.Indeed, over time, doctors/clinicians can come to associate certainbiomarkers with desired therapeutic effect, and therefore use suchmarkers for the analysis of the VOAs of the patient population.

In an example embodiment, location-specific data on brain response torespective VOAs, for example as indicated by changes tolocation-specific biomarkers in the brain, is aggregated over a largenumber of patients. For treatment of a new patient, the system isconfigured to obtain biomarkers characterizing a current brain state ofthe patient. The system is configured to obtain biomarkers representinga desired brain state for the patient. The system is then configured toautomatically determine and output a target volume of activationestimated as most likely to achieve the change in brain state from thecurrent brain state to the desired brain state. For this determination,the system is configured to search the library of VOAs and thecorresponding aggregated location-specific brain response data todetermine which VOA has been shown to produce the response which providethe desired change.

For example, in an example embodiment, information of a new patient,including a corresponding. e.g., novel, indication is entered. Abiomarker is found. Brain states are searched. The system thenidentifies the brain state which would abolish the biomarker. The systemthen identifies the VOA associated with that brain state, e.g., the VOAwhich would produce the desired change from the current brain state toproduce the identified target brain state. The system then provides thatVOA (and associated stimulation settings) as a target volume fortreating the entered indication.

6. Filtering VOAs Based on Medications or Time of Day:

The medication a patient is on and the time of day when stimulation isperformed can affect stimulation results. According to an exampleembodiment, the system filters the VOA groupings by the medicationswhich the patient records indicate the patients, to whom the respectiveVOAs correspond, to have been on at the time of the stimulation. Forexample, a user can input a medication which a current patient is on,and request a target stimulation volume based on region/voxelcombinations of VOAs corresponding to patients on the same medication(and/or dosage). In an example embodiment, the system is configured toconsider medication concentration, type, and/or state.

According to an example embodiment, the system filters the VOA groupingsby the time of day when the stimulations corresponding to the VOAs wereperformed. For example, a user can input a time of day (e.g., morning,afternoon, early evening, night), and request a target stimulationvolume based on region/voxel combinations of VOAs corresponding tostimulations performed during the relevant time period.

Thus, example embodiments provide for use of a plurality of parametersas filters for analytics. Time or medication concentration/type/stateare usable to refine analyses. For example, unfiltered data may show aweak correlation between a particular stimulation volume and an effect,but, upon filtering by time, the data may show a strong correlationbetween the stimulation volume and the effect when the stimulation isperformed in the morning. In an example embodiment, the system isconfigured to use the filtered analyses to inform future programsettings to compensate for changes in time. Similarly, other potentialparameters for filtered analyses include, for example, demographics,health state, body position, and/or disease type or subtype.

7. SFM Analysis for Target Volume Generation Based on Selected ClinicalEffects:

VOAs can be generated for a plurality of patients of a patientpopulation, and each of all or a subset of the VOAs can be recorded inassociation with one or more therapeutic effects and/or adverse sideeffects. In an example embodiment, the system provides a user interfacevia which a user. e.g., a clinician, can select one or more therapeuticeffects, in response to which the system outputs a target volume forachieving the indicated combination of effects based on analysis of theVOAs of the patient population and the therapeutic effects with whichthey are associated, where only those VOAs which are associated with theindicated therapeutic effects are selected. The system then outputs avolume formed by the overlap of those VOAs or formed of the voxels thatare in a significant number of the VOAs associated with that therapeuticeffect. In an example embodiment, the system provides a user interfacevia which the system is configured to receive user input of a thresholdnumber or threshold percentage of considered VOAs in which a voxel mustbe found to be included in the returned area.

Similarly, according to an example embodiment of the present invention,the system provides a customized side effect volume showing regions toavoid, based on user selected adverse side effects, where the systemreturns a side effect volume formed by the overlapping of VOAsassociated with the indicated side effects, e.g., subtracting therefromregions in VOAs not associated with the adverse side effects. Accordingto an example embodiment, the user can input both therapeutic effectsand adverse side effects to consider, and the system produces a newtarget volume formed by the overlap of the VOAs associated with theindicated therapeutic effect minus portions associated with the volumesassociated with the indicated adverse side effects. Similar to thatwhich is described above, in an example embodiment, the system providesa user interface via which the system is configured to receive userinput of a threshold number or threshold percentage of considered sideeffect VOAs in which a voxel must be found to be considered as belongingto the side effect area.

For example, a user can input a desired primary effect, in response towhich the system suggests one or more stimulation target volumes and/orassociated stimulation parameters. The user can continually modify andrefine the desired effects. For example, the user can input a requestfor more of a particular clinical effect and/or avoidance of additionalside effects, in response to which the system outputs a modified target,until finally the system outputs a suggested final target volume orfamily of volumes of a circuit.

In an example embodiment, various target effects/structures can be usedto guide a trajectory through multiple targets. Select a series ofdesired effects, and the system, in an example embodiment, shows one ormore trajectories through multiple targets that may have disparateresults related to the desired effects.

In an example embodiment of the present invention, a user can inputstimulation program settings in response to which the system outputs adisplay in the graphical user interface (GUI) a map of neighborhoodeffects showing the respective next change in effects associated with achange in the VOA position, in each of a plurality of directions, fromthe current VOA position. For example, For example, FIG. 12 shows anexample of a neighborhood effects map 1200 with labels 1202, 1204, 1206,1208 indicating the change in an effect with a change in the VOA 1210position. In an example embodiment, users can build the neighborhoodeffects probability atlases, and the users can export, share, and importthem.

8. Clinical Effects Analysis for Target Stimulation Time and/orMedication Determination:

According to an example embodiment, the system analyzes the effects ofstimulations against time of day to determine a target stimulation time.For example, the system creates a histogram of stimulations by time ofday (e.g., morning, afternoon, early evening, night) to determine if aparticular therapeutic effect or side effect is statisticallysignificantly associated with a particular time of day, and, if so,outputs such information. This information can differ for differentconsidered therapeutic effect and/or side effects. According to anexample embodiment, the system provides an interface in which the usercan select combinations of therapeutic effects and/or side effects, andthe system determines whether there is a statistically significant timeperiod association for that indicated combination, in which case, thesystem outputs a recommended time of day for therapy.

Medications taken by respective patients with which the stimulations areassociated can be considered in a similar manner to determine arecommending medicinal regimen to follow during the period whenstimulation is performed.

The affect that time of day and/or medication has on the clinicaleffects may be dependent on the particular areas stimulated and/or thedemographics of the patients subject to the respective stimulations.Thus, according to an example embodiment, the system tests thestatistical significance of time of day and/or medication againstdifferent stimulation areas and/or demographics. Thus, different timesof day and/or medications can be recommended for different stimulationregions and/or for different patient demographic information.

9. Analysis of VOA Overlap with Target Volume:

According to an example embodiment of the present invention, the systemis configured to quantify the extent to which a VOA meets a targetvolume based on a spatial difference of the VOA and the target volume.For example, the extent to which the VOA extends beyond the targetvolume, the extent to which the target volume extends beyond the VOA,and the extent to which the VOA and the target volume overlap contributeto an overall score of the VOA. Sec, for example, U.S. ProvisionalPatent Application Ser. Nos. 61/521,572, filed Aug. 9, 2011 and61/549,053, filed Oct. 19, 2011, the entire content of each of which ishereby incorporated by reference herein.

According to an example embodiment of the present invention, the systemis configured to determine how well a group of VOAs meets a targetvolume. For example, the system determines a spatial difference betweenthe group of VOAs and the target volume. For example, the system assignsto each VOA of the group a score indicating how well the respective VOAmeets the target, and a combination of the scores can be used as ametric to determine how well the group meets the target volume. Forexample, a particular set of parameter settings might be common to allof the VOAs of the group, and it may be useful to know the extent towhich the settings are expected to produce a VOA that substantiallymeets the target volume. The score can be used as a metric of theexpectation.

Alternatively or additionally, the determination of the extent to whichthe group of VOAs corresponds to the target volume can be performed forthe VOAs as a whole, by which the system calculates a mean and/orstandard deviation to rate the VOAs as a group.

According to an example embodiment, the system outputs a numberindicating how many or the percentage of the VOAs of the group that meeta certain threshold correspondence with the target volume.

According to an alternative example embodiment, for each point that isincluded in any of the VOAs of the group, the system determines thenumber of the VOAs of the group in which the point is included andincludes the point in a composite volume if the point is determined tobe included in a threshold number or percentage of the VOAs of thegroup. The system compares the composite volume to the target volume andscores the composite volume based on the degree of similarity betweenthe target and composite volumes. The system outputs the score as arating of the correspondence between the group of VOAs and the targetvolume.

According to an example embodiment of the present invention, asimilarity of an average center of mass of the group of VOAs and thecenter of mass of the target volume is a factor used by the system tocalculate the rating of the correspondence of the group of VOAs to thetarget volume.

10. SFM Analysis for Patient-Specific Atlas Generation:

According to an example embodiment of the present invention, the systemanalyzes VOAs of a plurality of patients to create a new patientpopulation group for obtaining an average atlas to be registered to anew patient. e.g., as described in the '232 application. Cliniciansprogram a leadwire implanted in a patient to obtain certain therapeuticeffects, while avoiding adverse side effects as much as possible.Different patients will require different volumes of tissue to beactivated for achieving results tailored to that respective patient,because different patients need different therapies and because, evenfor a same therapy, different patients can require differentstimulations for achieving the same desired results. If, despite thetailoring of parameters and VOAs to achieve customized patient-specificresults, the VOAs of a group of patients are similar, in an exampleembodiment, the system forms a new patient population group, which isthe group of patients with whom the similar VOAs are associated. Forexample, in an example embodiment of the present invention, the systemcompares the VOAs to each other to find significant overlap and/or lackof significant spill. For example, in an example embodiment, forcomparison of the VOAs of the patient population to each other, thesystem uses one or more equations described, for comparing a VOA to atarget volume, in U.S. patent application Ser. No. 13/570,736 filed Aug.9, 2012, which claims priority to U.S. Prov. App. Ser. Nos. 61/651,282filed May 24, 2012, 61/549,053 filed Oct. 19, 2011, and 61/521,572 filedAug. 9, 2011, all of which are incorporated herein by reference in theirentireties. Alternatively, the system can use an Overlap Ratio Measure,for example as described in Siegel et al., “Spatiotemporal Dynamics ofthe Functional Architecture for Gain Fields in Inferior Parietal Lobuleof Behaving Monkey,” Cerebral Cortex 17(2), pp. 378-390 (February 2007),the contents of which is incorporated by reference herein in itsentirety.

In an example embodiment, if the system finds a group of patients withinthe patient population whose successful VOAs are similar, for examplebased on the mentioned comparisons, the system generates a new patientpopulation group the members of which are the patients whosecorresponding VOAs have been determined to be similar.

In an example embodiment, the new patient population group is used forobtaining a customized atlas for registration to a new patient, e.g., asdescribed in the '232 application. For example, the system determinesrecorded characteristics, e.g., indication, age, sex, geographiclocation, medications being taken, etc., of the patients of the newpatient population group which are shared by all or a thresholdpercentage of the new patient population group. If characteristics of anew patient match those characteristics (or a significant number ofthose characteristics), the system uses an atlas from that new patientpopulation group to register to the new patient, e.g., to a medicalimage of the new patient. Alternatively, a doctor, surgeon, and/orclinician can view the characteristics associated with various patientpopulation groups and, for example, based on such information, manuallyselect the patient population group to use for obtaining an atlas toregister to the new patient. The atlas of the patient population groupused for registration to the new patient can be, for example, an averageof the atlases of the patient population group, and average medicalimage of the patient population group (e.g., normalized to a commonreference coordinate system), or an atlas generated based on the averageimage.

According to an example embodiment, the group can be further divided bynoted associated therapeutic effect. For example, if of 100 similarVOAs, 50 are associated with a first therapeutic effect and 50 areassociated with a second therapeutic effect, then according to anexample embodiment, the system generates a first patient populationgroup formed of the patients associated with the first 50 VOAs andgenerated a second patient population group formed of the patientsassociated with the second set of 50 VOAs. For atlas registration, thesystem (or clinician/doctor/surgeon) can select the set associated withthe therapeutic effect which is desired to be achieved in the newpatient.

According to an example embodiment, the system may similarly form newpatient population groups based on similarities in recorded adverse sideeffect volumes. For example, if VOAs of a plurality of patients whichwere associated with side effects are recorded, the system is configuredto, in an example embodiment, group those patients into a new group,which are then selected for use to create a patient-specific atlas for anew patient, based on similarities between the characteristics of thenew patient and that patient population group. As described above, thesegroupings can be further divided according to type of side effect.

According to an example embodiment of the present invention, the systemuses a lack of similarity of VOAs as a factor to determine whether tocreate a new patient population group. For example, if a group ofpatients have certain commonalities, e.g., one or more of age, race,geographical location, indication, medications takes, etc., whichcommonalities would suggest that similar VOAs should be used for thosepatients, but instead the VOAs for those patients actually break downinto two or more groups, where the VOAs in the same one of the groupsare similar, but are significantly different than the VOAs in the othergroups, then the system forms a new patient population group for each ofthose groups of VOAs. When an atlas is to be generated for a newpatient, in an example embodiment, the system compares an image of thenew patient to, for example, average atlases or images of each of thegroups, and selects the average atlas or image of the group most similarto the image of the new patient, for registration to the patient forgeneration of the patient-specific atlas.

Thus, as shown in FIG. 6, during a clinical stage 602, a user. e.g., adoctor, patient, clinician, etc. can use a stimulation programmingmodule (or modules) to set stimulation settings to stimulate ananatomical region of a patient. Many users can do this for manypatients, e.g., at a same or at a plurality of terminals. The module isconfigured to generate estimated VOAs corresponding to the stimulationsettings. The module is further configured to receive user and/or sensorinput regarding clinical effects of the stimulation, which the systemstores in association with the respective VOA on a cloud-based datastore. The system is further configured to obtain additional patientinformation, e.g., from an electronic medical file, with whichinformation the VOA is associated. An analysis module 604 performsanalyses on the plurality of VOAs, the associated clinical effects,and/or the associated patient information, to refine target and sideeffect volumes. The user of the programming module can then access therefined target and side effect volumes 606 for tailoring stimulationsettings of subsequent stimulations for a plurality of patients. Thetarget and side effect volumes used for the subsequent stimulations canbe based on a filtered set of the prior VOAs. e.g., which set is mostrelevant to the respective patient to whom the subsequent stimulation isbeing applied. However, aside from use of the VOA analytics to refinetarget and side effect volumes, in an example embodiment, the system isconfigured to identify clusters of patients of the patient populationbased on the respective VOAs associated with respective ones of thepatients of the patient population, and identified relationships betweensuch VOAs, where the clusters form respective patient population groupsfor which respective atlases are provided.

For example, FIG. 10 illustrates an example where the data storeincludes VOAs corresponding to stimulation programs set for patientsA-D. MRIs of the brains of patients A-D, and other medical recordinformation concerning patients A-D. In the illustrated example, thesystem identified an overlap between the VOAs associated with patients Aand B, and identifies an overlap between the VOAs associated withpatients C and D. The system therefore generates Cluster 1 formed ofpatients A and B, and combines data of the MRIs of patients A and B toform Atlas 1 for Cluster 1; and generates Cluster 2 formed of patients Cand D, and combines data of the MRIs of patients C and D to form Atlas 2for Cluster 2. The system also identifies characteristics. e.g., medicalrecord characteristics, shared by patients A and B and characteristicsshared by patients C and D, and associates the respective sharedcharacteristics with the respective clusters.

The system is configured to provide user interfaces for stimulationprogramming and visualization in which the system outputs a graphicalrepresentation of an implanted leadwire and/or stimulation volumes, suchas estimated VOAs, target volumes, and/or side effect volumes, relativeto anatomical structures of the patient, where those anatomicalstructures are spatially arranged according to a patient-specificanatomical atlas. Therefore, when a new stimulationprogramming/visualization electronic record for a patient is generatedincluding the patient information used for outputting patient-specificstimulation volume information, the system is configured to store in theelectronic record the patient-specific atlas. To do so, in the exampleillustrated in FIG. 10, the system is configured to select one aplurality of patient population atlases for registration to the newpatient. In FIG. 10, the system compares characteristics. e.g., medicalrecord characteristics, which can include, for example, demographics, ofnew patient E to the respective characteristic sets associated with eachof Clusters 1 and 2. In the example shown in FIG. 10, the system hasdetermined that the characteristics of new patient E are most similar tothose associated with Cluster 2, and the system therefore selects Atlas2 of Cluster 2 and registers it to anatomical information, e.g., an MRIof new patient E to generate a patient-specific atlas for patient E.

In an example embodiment, referring to the example illustrated in FIG.10, subsequent to applying stimulation programs to patient E, patient Ecan be added to the patient population, and the system is configured tofurther modify the previously generated clusters in view of VOAsassociated with patient E, for example to add patient E to one of thepreviously generated clusters, to add a new cluster, and/or to breakapart one or more previously generated clusters. Thus, the patientpopulation clusters can evolve over time. With each change to thepatient population clustering, the system can generate a new respectivepatient population atlas for each new and/or modified cluster, which thesystem is configured to use for later generation of patient-specificatlases for newly added patient records. In an example embodiment, thesystem is configured to update even the patient-specific atlasespreviously generated for patients. e.g., even ones previously includedin a cluster, based on a modification to the patient populationclusterings.

11. Patient-Specific Atlas Generation Based on a Hierarchy of Images orAtlases of a Patient Population:

According to an example embodiment of the present invention, take theMRI of many patients and either using the whole MRI or regions ofinterest within it (e.g., Basal Ganglia), cluster the images (orcorresponding atlases) using some metric of image similarity, e.g., tocreate a hierarchy of medical images or atlases. For example, theclustering of the database images may be done hierarchically so as toobtain a cluster tree, where, at the bottom of the tree, the individualimages are the leaf nodes, which can then branch upward to a node of ahigher hierarchical level. The nodes of the higher hierarchical levelscorrespond to a template constructed based on the images/templates ofnodes of the branches below the respective node.

In an example embodiment, the hierarchical tree is used for efficientlyfinding an image/atlas to register to a new patient. For example, thesystem compares an image of a new patient to the average image/atlas ofthe nodes beginning with the top hierarchical level, working downwardsuntil branch by branch, at each level selecting the node with thegreatest match, until selecting the best leaf node. In this manner, thenew patient's image need not be compared to each leaf node to find thebest match. The selected leaf node's atlas can then be registered to theimage of the new patient to form the patient-specific atlas. This mayenable an efficient search for similarity between the patient and thecandidates.

In an example embodiment, the system selects from the hierarchy the ‘n’closest MRIs transformed to a common space, e.g., Montreal NeurologicalInstitute (MNI) space and/or takes the average MRI (or othermathematically constructed MRI combination) that best represents the ‘n’MRIs, and the system registers the selected MRI/Atlas for registrationto the new patient's medical image.

12. Interface for User Input of Logical Combinations of SFMs for Targetand/or Side Effect Volume Generation:

According to an example embodiment, the system provides a user interfaceby which the user can select characteristics to consider when generatinga target and/or adverse side effect volume, and to also select a logicaloperator to use for the generation of the new volume. For example, theuser can input an instruction to a return a new volume based on alltherapeutic VOAs associated with one or more therapeutic effects and/orone or more identified patient characteristics with which the VOAs areassociated, and further select an operator such as union or intersect.For example, the user can select a union of VOAs of a certain type, inresponse to which the system returns a volume composed of thecombination of areas in the relevant VOAs, or the user can select anintersection of volumes, in response to which the system returns avolume composed of the areas found in all (or a threshold percentage) ofthe relevant VOAs. Another logical operation can be NOT, where the usercan indicate certain VOAs not to be considered (for example not VOAsassociated with particular specified patients, not patients ofparticular specified doctors, and/or not patients of a certaindemographic, etc.; and/or the reverse, only VOAs associated withparticular specified patients, only patients of particular specifieddoctors, and/or only patients of a certain demographic, etc.) or wherethe user can indicate areas to be removed, e.g., remove from the unionor intersection those areas that are also found in VOAs associated withcertain specified adverse side effects. The user can similarly select tohave a side effect volume returned, formed by the combination (e.g.,union or intersection, as specified) of VOAs associated with certainspecified adverse side effects.

According to an example embodiment, the system further allows input ofmultiple logical operators such as a combination of both union andintersection. For example, the user can input an instruction to return avolume formed of the intersection of (a) a first group of one or moreVOAs with (b) the union of VOAs of a second group, in response to whichthe system would find the area formed by the union of the second group,and find the area formed by the intersection of that union area with thearea within the VOAs of the first group.

Thus, the system provides a user interface which includes a toolset bywhich a user can define how the system generates new volumes which theuser can then use. e.g., for a current patient, for example, to setstimulation parameters of a current patient.

13. Other Analyses:

SFM analyses can include analysis of variance (ANOVA), generalizedlinear models, parametric or non-parametric techniques, Bayesiananalysis, etc.

Obtaining Analysis Paradigms and/or Data for Analysis

According to an example embodiment of the present invention, the systemincludes features by which to collect VOA related data over time to thenbe subject to an analysis, for example, one or more of the analysesdescribed above. According to an example embodiment, the system isconfigured such that, where a user begins compilation of a parameter setof an analysis to be conducted on an input set of data, e.g., an inputset of VOAs, as described above, the user is able to save theconstructed analysis paradigm and retrieve it a later time, e.g., formodification and/or application to a set of data input. In an exampleembodiment, a saved analysis paradigm may function as a template, e.g.,which can be copied as a new analysis paradigm, which copy can befurther modified. Moreover, the data collection to which an analysis isapplied can be a parameter of a saved analysis paradigm. A template canbe copied multiple times, and modified to be applied to different setsof data.

In an example embodiment, an analysis template can be saved withoutspecification of a data collection to which the analysis is to beapplied. Such a template can be copied as a new analysis record andmodified to specify the data collection on which the analysis isperformed and to include results of such an analysis. Multiple copiescan be saved, each specifying, for example, a different data collection.

For example, an analysis paradigm can be set up by which to find spatialdifferences between two different types of groups. Group A data set andGroup B data set. Further, the analysis can be set with, for example,certain thresholds to rate the data (e.g., threshold overlap orthreshold difference), certain statistical tests to be applied, etc.Thus, there can be a number of parameters to use for an analysis. Such aparadigm specifying one or more of such variable parameters can be savedas a template, and copied as new analysis paradigms to which to applydifferent data sets or modified analysis parameters, for which a usercan select an activation instruction, in response to which the systemruns the modified analysis on the respectively specified data. Forexample, the system may display a “run” button in a GUI, in response toselection of which, the system runs the specified analysis.

According to an example embodiment, the templates can be stored as adata structure that can be shared by users. For example, in an exampleembodiment, a template can be attached to an e-mail which one user cansend to another user, which other user can open and modify or otherwiseuse the attached template, e.g., where the other user also includes thesoftware adapted to interpret the data structure. Alternatively oradditionally, the template can be stored in a central locationaccessible by a plurality of terminals on which the software is run. Inan example embodiment, the data collection, e.g. VOAs and/or associatedstimulation parameters, to which the analysis is applied can also beshared e.g., separate from the template and/or as part of the template.

According to an example embodiment of the present invention, the systemis configured for storing associated groups of data. e.g., groups ofVOAs and/or associated stimulation parameter sets, which groups can beopened by a user to be subjected to various analyses. The groups canfurther be modified over time. For example, in an example embodiment,the system includes an interface. e.g., a graphical user interfaceand/or other interface, via which to receive user input for specifying aset of stimulation parameters and/or associated VOAs, and/or via whichto output the set of stimulation parameters and/or graphicalrepresentations of such VOAs. The system further includes, according toan example embodiment, a selectable menu item, such as an option of a“File” menu selectable from a toolbar, which, when selected allows theuser to save the presently open stimulation settings and/or VOA to adatabase folder representing the group. If no folder representing thegroup has been previously set up, or if the user otherwise wants a newgroup, the system allows the user to select “New Folder” or “New Group”or the like to create the folder/group with which to associate the opensettings and/or VOA.

In an example embodiment of the present invention, the system displaysin a GUI selectable graphical representations of groups that have beenpreviously created, provided for user selection to associate a set ofstimulation parameters and/or a VOA that is in focus with the selectedgroup representation. In an example embodiment, the set of settingsand/or VOA can be added by drag-and-drop. For example, an iconrepresenting the set of settings and/or VOA that is in focus. e.g., thatis displayed, is selectable and can be dropped onto one of the grouprepresentations to be included as part of the group. Each stored groupcan be separately subjected to one or more analyses. In an exampleembodiment, the system also includes an icon for creating a new group,which is selectable and/or to which a set of stimulation settings and/ora VOA can be dropped, in response to which selection or drop, the systemprovides for a user interaction by which to name a new group to whichthe set of settings and/or VOA that is in focus can be added.

For example, as a clinician notices various symptoms associated with aparticular VOA, the clinician can use the GUI features to drop the VOAinto various “buckets” that can later be used for analysis. For example,the clinician notices eye movement, and therefore associates the VOA infocus with a bucket of VOAs that resulted in eye movement. In thisregard, a VOA and/or a set of stimulation settings can be associatedwith more than one data group, and can be subjected to analyses of suchdifferent groups and/or subject to different types of analyses. At anypoint in time, a user can use the system to subject such a bucket to ananalysis, during which the system performs an analysis, e.g., asdescribed herein, on those volumes that are included in the bucket. Itis noted that the system can similarly maintain buckets of side effectvolumes and target volumes on which analyses can be run.

Various kinds of data can be associated with VOAs (or other volumes), bywhich the VOAs (or other volumes) can be filtered. Such data caninclude, for example, diagnosis, age, gender, medication used, clinicaltest scores, patient assessment of well being, target volume with whichthe VOA and/or stimulation settings are associated, variance of amedical image of a patient with which the VOA and/or stimulationsettings are associated from a standard atlas, quantitative data from ameasurement device such as an accelerometer, of a sensor whose signalscan have a certain significance, e.g., indicating tremor, straightnessof lines, dwell time, etc. According to an example embodiment, a usercan filter stored VOAs (or other volume types) and/or sets ofstimulation settings by such data, and apply the filtered group to ananalysis. For example, with respect to variance between medical imageand standard atlas, a user might want to filter out those VOAs and/orsettings that are associated with a patient whose medical image(s)varies from a standard atlas by a threshold amount, since results of astimulation applied to such a patient may be expected to be differentthan those normally expected from a patient whose anatomy more closelycorresponds to the typical anatomical arrangement. Aside from enteringfilter parameters for obtaining a matching set of volumes to beimmediately subjected to an analysis, the system is also configured toprovide for filtering of the volumes to obtain a filtered set that canbe stored as a new bucket, which can later be retrieved. e.g., forrunning one or more analyses.

Creation and Sharing of Target Volumes

According to an example embodiment of the present invention, a system isprovided that provides for a cycle of testing stimulation settings thatproduce corresponding VOAs, obtaining results of such tested settings,analyzing such results, selecting a refined target volume based on suchanalyses, and selecting new stimulation settings to be tested. A refinedvolume can be selected. e.g., by changing the volume's position,orientation, size, shape, etc. Moreover, in an example embodiment, suchmodifications can be performed graphically. e.g., by manipulation ofgraphically displayed nodes.

This cycle can be repeated, e.g., continuously, to refine thestimulation settings. Moreover, the testing can be of stimulationsettings of a plurality of patients and the analyses can be of resultsof such tested settings and/or their corresponding VOAs of a pluralityof patients.

For example, information concerning such settings, their correspondingVOAs, and respective results of stimulations using such settings can bestored at a single location for access by one or more clinicians who canset new target volumes and/or choose modified target stimulation regionsbased on results of the analyses. FIG. 6 illustrates the stimulation andanalysis cycle by which target volumes and/or stimulation settings canbe refined.

FIG. 7 shows a modified cycle according to an example embodiment of thepresent invention, according to which users are able to share and/orpublish their discovered and/or input target volumes for implementationby other users. For example, at a step 700, a guide module can transmitstimulation settings to an IPG for application of those settings toelectrodes of an implanted leadwire to stimulate an anatomical region ofa patient. At step 702 an analysis can be performed on the testedsettings, corresponding VOAs, and/or results of such stimulations,tested by one or more clinicians on one or more patients. At step 704, auser can select a new target region based on the analysis, and share itwith a community 706 of users, e.g., clinicians, researchers, and/orother users, who can use such a shared target region to select newstimulation settings to test at 700.

Referring to FIG. 8, according to an example embodiment, at step 800, afirst doctor, “Dr. A.” uses a Guide module on a workstation, to setstimulation parameters, view a corresponding VOA, apply the settings toan IPG and an implanted electrode leadwire, and/or record results ofsuch stimulation settings.

At step 802. Dr. A selects a target volume based on the results of theapplied stimulation settings. (It is noted that a different doctor mayinstead select the volume. It is also noted that the newly selectedvolume can be based on analysis of results of settings applied to morethan one patient by more than one doctor. It is also noted that theselection of the new target volume can be further based on results of aplurality of different applied sets of stimulation settings. It is alsonoted that the analysis can be manual or can be automatic, e.g., usingone or more of the analyses described above.)

At step 804, the Guide module generates a code for the target volume setby Dr. A. For example, Dr. A selects an option to save the input targetvolume and the system responsively generates and outputs a codeassociated with the saved target volume. For example, Dr. A can save thetarget volume under any descriptive name by which Dr. A can lateridentify the target volume in a useful manner, but the system can storea field, that includes the generated code, in association with the savedtarget volume. Further, in an example embodiment, the field can beopened for view by Dr. A so that Dr. A can later identify the code ifotherwise forgotten. For example, in an example embodiment, responsiveto right-clicking a representation of a file corresponding to the targetvolume, the user is able to view properties of the file, including thegenerated code. Alternatively, when the target volume is opened by Dr.A, the system also displays the code. (In an alternative exampleembodiment, the doctor manually enters a code, and the system isconfigured to inform the doctor whether the entered code is available.)

At step 806. Dr. A shares the code with one or more other doctors. Forexample. Dr. A e-mails the code or otherwise publishes the code. At step808. Dr. B inputs the code into an instantiated Guide module running onDr. B's terminal, in response to which, at step 810, the Guide moduleinto which Dr. B input the code displays or otherwise uses the targetvolume selected by Dr. A and for which the code was previouslygenerated. For example, in an example embodiment target volumes areaccessible via an alphanumeric code that is published so that otherusers can then use the code to access a central server that providesthem with the target volume, e.g., they can be downloaded via a webpageof the cloud.

In an example embodiment, when other users import such publishedvolumes, the system provides for the importing user to tag the importedvolume, for example, with data identifying who generated the volume, inwhich facility the data was generated, etc., and to store the taggedvolume in a folder owned by the importing user. In an alternativeembodiment, the system is configured to automatically append suchmetadata, e.g., which can be accessed by the importing user.

The target volume selected at step 802 can be generated manually by Dr.A, e.g., by manipulation of graphical nodes in a user interface, or canbe generated automatically by the system based on input. e.g., selectedby Dr. A. For example, Dr. A can input a group including a plurality ofsets of stimulations settings, corresponding VOAs, and results into asystem-run analysis. e.g., one of the analyses described above, based ontarget generation parameters (pre-programmed and/or user input) of whichthe system outputs the target volume, which Dr. A can select for saving.

Dr. A can store a plurality of target volumes. For example, differentones of the stored target volumes can be associated with differentgroups of patients. For example, different target volumes can beassociated with different desired therapeutic effects, differentdiseases, different indications, etc. In an example embodiment, thesystem enables the user to identify the characteristic with which thetarget volume is to be associated. For example, a file name or foldername can be used to identify the characteristic.

While the above discussion concerning sharing of volumes, e.g., inconnection with FIG. 8, has been described with respect to targetvolumes, in an example embodiment, the system also provides for a userto likewise share side effect volumes. For example, Dr. A can manuallyenter a side effect region where stimulation is to be avoided or thesystem can automatically generate a side effect region, e.g., asdescribed above in the “Group Comparisons” section. The system canassign a code to the side effect region, which code can be shared asdescribed above with respect to the target volumes.

In an example embodiment of the present invention, the system stores theuser-defined/selected target and/or side effect regions at a centrallocation accessible by a plurality of terminals running a Guide module.It is noted that a number of users can also use a single terminal usingdifferent log-in information. The different users of the same ordifferent terminals can thereby obtain, from the central location andvia a network, e.g., the Internet, the stored target and/or side effectregion previously selected by a different user. The user can identifywhich volume to obtain by entering the corresponding code.

In an alternative example embodiment, the system generates a code forthe selected target or side effect volume based on characteristics ofthe volume. In an example embodiment, the generation of the code basedon the characteristics of the volume is such that the system is able toreconstruct the volume based on the code. For example, the code may bebased on one or more of a center of mass of the volume and spatialcoordinates of a perimeter of the volume. Other characteristics of thevolume as described above with respect to data stored to represent avolume can additionally or alternatively be used. Accordingly, thevolume need not be stored. Instead, a user can share a selected volumeby sharing the code generated by the system, and another user can enterthe shared code, in response to which the system outputs the volumereconstructed based on the code.

In an example embodiment, when a first user, using the Guide software toprogram a system, enters a code to open a volume shared by a seconduser, the system is configured to modify the shared volume to reflect ananatomy of the patient. For example, the shared volume might have beengenerated in a space corresponding to the brain of a different patientor in a generic atlas space, which varies from the anatomical spacecorresponding to the brain of the currently active patient information.

In an alternative example embodiment the system initially opens thevolume according to the spatial environment in which it is saved oraccording to a generic atlas space (even if the volume was generated inrelation to an anatomical space of another patient), and subsequently,in response to a user conversion instruction, transforms the volume toreflect the anatomy of a currently active patient. According to theembodiment in which the code is automatically generated based oncharacteristics of the volume, in an example embodiment the system isconfigured to, when a user selects to open the shared volume, open thevolume in a generic atlas space, and the user can instruct the system toconvert the volume to the patient anatomical space.

The volume being shared can be stored by the system in a manner by whichit is not associated with any patient for whom the shared volume wascreated, in order to preserve the patient's privacy. For example, asnoted above, even if the volume is generated in relation to ananatomical space of a patient, the system can be configured to outputthe shared volume transformed to a generic atlas space. Alternatively,the patient-specific anatomical space can be output since it cannot beused to easily identify the patient.

The system thus facilitates a continuous cycle of refinement of volumes.For example, a first clinician can open a number of target volumesselected by one or more other clinicians based, for example, on similarfindings reported by the one or more other clinicians. The user can thenhave the system run an analysis to find overlapping regions of themultiple target volumes, as discussed above, to thereby form a furtherrefined target volume.

In an example embodiment of the present invention, the system furtherincludes an option to automatically generate a target volume based on acombination of VOAs that correspond to the multiple selected targetvolumes. For example, in response to receipt of user input selecting theoption to generate the target volume based on the underlying VOAs, thesystem is configured to find for each of the selected target volumes abest fit set of stimulation variables to provide a respective best fitVOA. The best fit parameter settings and VOA can be patient-specific toa currently active or selected patient. The system then performs theanalysis upon the plurality of VOAs to find a new target volume (forwhich the system is configured to also find a further set of best fitparameter settings and corresponding VOA).

Alternatively, the user can have the system graphically overlap themultiple selected target volumes of the one or more other clinicians orthe corresponding best VOAs, and manually outline a new target volumebased on the displayed overlap.

Web Forum

According to an example embodiment of the present invention, the systemincludes a server to which system users' volumes are uploaded. A usercan create a new web group maintained by the server and invite/add otherusers to the user-hosted group. Those other users who accept/join thegroup are then able to view and use volumes shared with the group byother members of the group.

Target Volume Creation (Moving Results to Clinic)

Analysis results can be used to generate target (visualization) volumesfor both benefits and side-effects. Target volumes can be saved as amesh or a point (e.g., a centroid with additional information asdescribed above).

In an example embodiment, a target volume is definable by a selectedpoint about which the volume is to be draw n and a volume size. (Anglescan further be used to define an orientation of the target volumerelative to axes of an anatomical space.) For example, in an exampleembodiment, the system is configured to identify an average center ofmass of a selected plurality of VOAs. For example, the system isconfigured to provide a user-selectable option, in response to selectionof which the system is configured to calculate the average center ofmass of a set of VOAs selected by the user. The system is furtherconfigured to receive a size information and draw a target volumecentered on the calculated average center of mass and that is of thesize specified by the user.

In an alternative example embodiment, or as an additional alternativeoption, instead of an average center of mass of the VOAs, the systemfinds a respective average score for each of a plurality of voxels,where the average score for a voxel is an average of the scores of theVOAs in which the respective voxel is included. The score of a VOA canbe based on, for example, results of a stimulation to which the VOAcorresponds, as described above. In an example embodiment, the systemselects the voxel having the highest average score as the point aboutwhich to draw the target volume. Alternatively, the system finds acluster of highest average scoring voxels, and selects the center ofsuch a cluster as the point about which to draw the target volume. Theuser can manually enter a size, which the user might determine based ona general intuitive feel.

In an alternative example embodiment, or as an additional alternativeoption, the system first removes from consideration those VOAs having ascore below a predetermined programmed threshold, or a thresholdspecified by the user, and then finds the voxel having the highestaverage score (or center of a cluster of highest scoring voxels) of theremaining VOAs to set as the point about which to draw the targetvolume.

In an alternative example embodiment, or as an additional alternativeoption, the system first removes from consideration those VOAs having ascore below a predetermined programmed threshold, or a thresholdspecified by the user, and then finds the average center of mass of theremaining VOAs to set as the point about which to draw the targetvolume.

In an alternative example embodiment of the present invention, thesystem is configured to receive user input of a target volume size(e.g., as number of voxels, a radius, or any other suitablespecification of size), in accordance with which size specification thesystem is configured to adjust a score threshold to one that results inremoving just enough voxels to provide a volume approximately equal tothe specified size. Alternatively, the system is configured to receiveuser input of a target volume size (e.g., as number of voxels, a radius,or any other suitable specification of size), in accordance with whichsize specification the system is configured to adjust a score thresholdto one that results in removing just enough voxels to ensure that thespecified size is not exceeded. Alternatively, the system is configuredto receive user input of a target volume size (e.g., as number ofvoxels, a radius, or any other suitable specification of size), inaccordance with which size specification the system is configured toadjust a score threshold to one that results in removing just enoughvoxels to ensure that the specified size is not undershot. In an exampleembodiment, these described methods of adjusting a threshold inaccordance with a user-specified volume size are provided asuser-selectable options.

The threshold value can be a percentage, e.g., a user may require thetarget volume to encompass voxels that make up 80% of all the scores ofthe considered voxels. For example, the system is configured to receiveuser-input specifying a percentage, and to set the threshold such thatthe combined average scores of the remaining voxels (whose individualaverage scores meet the threshold) is equal to the specified percentageof the sum of the average scores of all considered voxels. That is, thevoxels of the output volume are such that

${\frac{\sum\limits_{i = 1}^{n\_ output}{{avg\_ score}{\_ of}{\_ voxel}_{i}}}{\sum\limits_{j = 1}^{n\_ input}{{avg\_ score}{\_ of}{\_ voxel}_{j}}} = {x\mspace{14mu}\%}},$where i is a voxel of the output volume, n_output is the number voxelsin the output volume, j is a voxel of one or more of the input volumes,n_input is the number of voxels that are included in at least one of theinput volumes, and x is the percentage specified by the user.Compatibility

In an example embodiment, the system is configured to providecompatibility modes in which to generate and/or analyze VOAs. The systemis configured to provide de-featuring in the compatibility modes. Forexample, data can be scaled down to render the data compatible withthird party analysis tools, to allow users to perform analysis from theperspective of the other systems.

In an example compatibility mode, the system turns off the ability tosimulate VOAs using multiple independent current or voltage sources, sothat only a single source is used for all contacts.

After turning off the relevant features, VOAs can then be generated asif they were done using the hardware and parameters supported by theother systems. Such VOAs can then be applied to a visualization,programming, or analysis tool.

As another example, certain systems allows for leadwire contacts to eachbe set to either on or off, while other systems allow for leadwirecontacts to each be set to a plurality of levels besides for on and off.e.g., 20% power, 30% power, etc. If a user is using a system of theformer type, the user can set the Guide and/or analysis modules to acompatibility mode in which contact settings can be set to only on andoff, and to lockout features not supported by the used hardware. In anexample embodiment, the user is presented with a checklist of featuresfor each of which the user can input whether the feature is supported bythe hardware being used.

Additional Feature:

Preop:

Using the Target and Side Effect regions, and additional constraints,automatically compute an optimal trajectory for implant.

Take the MRI of a plurality of patients and either using the whole MRIor regions of interest within it (e.g., Basal Ganglia), cluster theimages using a metric of image similarity. For generating a customizedatlas for a new patient, examine to which patients in the database thepatient is most similar. The system creates an atlas template for use inthe new patient's surgery based in the ‘n’ closest database MRIs. Theatlas can be created by transforming the ‘n’ closest MRIs to a standardspace, e.g., MNI space or it may be created by finding an “average MRI”that best represents the ‘n’ database MRIs. This may be accomplishedusing a variety of non-linear registration algorithms. The clustering ofthe database images can be done hierarchically so as to obtain a clustertree. At the bottom of the tree are the individual images, and at eachbranch the system can construct a template utilizing the images belowit. This enables an efficient search for similarity between the patientand the candidates.

Postop:

Aggregate VOAs across subjects using a standard space (e.g., MNI space)or within a new space which is the space of the average MRI that bestrepresents this subjects MRI.

Enable analytics by allowing clinicians to do “set theory” on the VOAs.For example, clinicians can compute voxels that are common to 1, 2, 3, .. . VOAs in the database. Each voxel is tagged by all the behavioralscores that its stimulation led to. For example, stimulation of a voxelin one patient may lead to low tremor, in another patient stimulation ofthe same voxel may lead to high tremor. Physicians can export this data,associating voxels with scores offline for their own analysis, but theycan also use the system to do analysis on the information.

For example, users can identify voxels whose activation significantlyaffects the stimulation using the following method. The system obtainsfor each voxel a series of scores, in the off (not activated) and on(activated) states. The system determines the difference between averagescores during the on and off states. The system permutes the on and offscores randomly and recomputes the difference. This is done 10,000 or sotimes, and the system plots a histogram of the scores to see where theoriginal difference sits in this histogram. The histogram is the nulldistribution. If the voxel influences the score significantly, the realdifference should be in the tail of the histogram. Definition of thetail requires a threshold, also known as a ‘p’ value. In an exampleembodiment, the system provides a user interface by which to specifythis threshold (e.g., 0.05, 0.1, etc.) which means that 5% of the valuesin the null distribution exceed this threshold or 10% exceed thisthreshold, respectively. The system can display either the voxels thatare in the tail according to a user specified threshold or the systemcan output to the user the ‘p’ value map itself as a false color 3D map.For example, in an example embodiment, the latter is displayed as falsecolor slices through a 3D space, for example overlayed on the MRI. Otherstatistical methods can be alternatively used.

According to an example embodiment, the system obtains the activatingfunction in the direction in which it is maximum at each voxel as anindependent variable and the behavioral score as an independent variableand determines which voxels show the most robust correlation between thebehavioral scores and the activating function magnitude. There are somevoxels for which high values of the activating function lead to negativevalues of the scores relative to baseline (symptoms improve), somevoxels for which high values of the activating function lead to positivevalues relative to baseline (symptoms worsen), and finally some voxelsfor which the activating function and the symptom improvement areindependent of each other. Thus, the system, according to this exampleembodiment, uses the correlation of the activating function and thescores to determine the effect of voxels on the considered clinicaleffect.

According to an example embodiment, for each stimulus setting, theelectric field distribution and the corresponding activation can becomputed using simplified models. If activation of a given region isdesired while avoiding affecting another region, an objective functionis used that maximizes the overlap with the region of desired activationand minimizes the overlap with the other region. Many objectivefunctions can be used. A difference of the overlaps may be the mostefficient. A search in parameter space can be performed to minimize theobjective function. Multiple search strategies are possible.

According to an example embodiment of the present invention, a largedatabase of lead contact positions, stimulus parameters, and outcomesare obtained and the system performs a machine learning exercise tomodel the dependence of stimulus parameters on the outcomes and thecontact positions.

The methods and systems described herein may be embodied in manydifferent forms and should not be construed as limited to theembodiments set forth herein. Accordingly, the methods and systemsdescribed herein may take the form of an entirely hardware embodiment,an entirely software embodiment or an embodiment combining software andhardware aspects. The methods described herein can be performed usingany type of processor or any combination of processors where eachprocessor performs at least part of the process. Systems referencedherein typically include memory and typically include methods forcommunication with other devices including mobile devices. Methods ofcommunication can include both wired and wireless (e.g., RF, optical, orinfrared) communications methods and such methods provide another typeof computer readable media; namely communication media. Wiredcommunication can include communication over a twisted pair, coaxialcable, fiber optics, wave guides, or the like, or any combinationthereof. Wireless communication can include RF, infrared, acoustic, nearfield communication, Bluetooth™, or the like, or any combinationthereof.

The methods disclosed herein can be implemented by computer programinstructions. These program instructions may be provided to a processorto produce a machine, such that the instructions, which execute on theprocessor, create means for implementing the actions. The computerprogram instructions may be executed by a processor to cause a series ofoperational steps to be performed by the processor to produce a computerimplemented process. The computer program instructions may also cause atleast some of the operational steps to be performed in parallel.Moreover, some of the steps may also be performed across more than oneprocessor, such as might arise in a multi-processor computer system. Inaddition, one or more processes may also be performed concurrently withother processes, or even in a different sequence than illustrated.

The above description is intended to be illustrative, and notrestrictive. Those skilled in the art can appreciate from the foregoingdescription that the present invention may be implemented in a varietyof forms, and that the various embodiments may be implemented alone orin combination. Therefore, while the embodiments of the presentinvention have been described in connection with particular examplesthereof, the true scope of the embodiments and/or methods of the presentinvention should not be so limited since other modifications will becomeapparent to the skilled practitioner upon a study of the drawings,specification, and the following claims.

What is claimed is:
 1. A method, comprising: obtaining atlasregistration information regarding a patient and obtaining a surgicaltrajectory for implantation of a leadwire; obtaining user input of atleast one desired therapeutic effect; obtaining effects of electricalstimulations performed on a plurality of patients of a patientpopulation; analyzing, by a processor, the effects of electricalstimulations performed on the plurality of patients of the patientpopulation to determine a plurality of volumes of activation (VOAs)along the surgical trajectory and utilizing the atlas registrationinformation, wherein each of the VOAs corresponds to an estimate of avolume of tissue stimulated using a corresponding set of stimulationparameters; scoring each of the VOAs to reflect production of the atleast one desired therapeutic effect by stimulation of the VOA; based onthe analysis and scoring, determining, by the processor, a target volumeand a corresponding set of stimulation parameters that are estimated toprovide electrical stimulation of the target volume; and stimulating thepatient using the corresponding set of stimulation parameters for thetarget volume.
 2. The method of claim 1, wherein obtaining atlasregistration information comprises identifying an AC-PC (anteriorcommissure-posterior commissure) in an image of the patient.
 3. Themethod of claim 1, wherein obtaining atlas registration informationcomprises obtaining an image of the patient and registering the image toan atlas.
 4. The method of claim 1, wherein obtaining atlas registrationinformation comprises comparing the patient to a plurality of populationgroups of the patient population, wherein an atlas is associated witheach of the population groups, and selecting the atlas of the populationgroup that is most similar to the patient.
 5. The method of claim 4,wherein obtaining atlas registration information comprises transformingan image of the patient to register the image to the atlas of thepopulation group that is most similar to the patient.
 6. The method ofclaim 1, further comprising obtaining user input of at least one sideeffect, wherein the scoring of the VOAs also reflects production of theat least one side effect by stimulation of the VOA.
 7. The method ofclaim 1, wherein determining the target volume comprises selectingpoints for the target volume that belong to a threshold number orpercentage of the VOAs.
 8. The method of claim 1, wherein determiningthe target volume comprises selecting points for the target volume thathave a threshold score based on the VOAs containing the point weightedby the scoring of the VOA.
 9. The method of claim 1, further comprisingfiltering the VOAs by a time of day when electrical stimulation of theVOA was performed.
 10. The method of claim 1, further comprisingfiltering the VOAs by a medication used by a patient associated with theVOA.
 11. A system, comprising: at least one computer processor; and amemory coupled to the at least one computer processor and havinginstructions stored thereon, wherein the instructions are configured toperform the following acts when executed by the at least one computerprocessor: obtaining a surgical trajectory for implantation of aleadwire; obtaining user input of at least one desired therapeuticeffect; obtaining effects of electrical stimulations performed on aplurality of patients of a patient population; analyzing the effects ofelectrical stimulations performed on the plurality of patients of thepatient population to determine a plurality of volumes of activation(VOAs) along the surgical trajectory and utilizing atlas registrationinformation, wherein each of the VOAs corresponds to an estimate of avolume of tissue stimulated using a corresponding set of stimulationparameters; scoring each of the VOAs to reflect production of the atleast one desired therapeutic effect by stimulation of the VOA; based onthe analysis and scoring, determining a target volume and acorresponding set of stimulation parameters that are estimated toprovide electrical stimulation of the target volume; and stimulating thepatient using the corresponding set of stimulation parameters for thetarget volume.
 12. The system of claim 11, wherein the at least onecomputer processor is configured and arranged to perform the followingadditional act: obtaining the atlas registration information regardingthe surgical trajectory for implantation of the leadwire.
 13. The systemof claim 11, wherein obtaining the atlas registration informationcomprises obtaining an image of the patient and registering the image toan atlas.
 14. The system of claim 12, wherein obtaining the atlasregistration information comprises comparing the patient to a pluralityof population groups of the patient population, wherein an atlas isassociated with each of the population groups, and selecting the atlasof the population group that is most similar to the patient.
 15. Thesystem of claim 14, wherein obtaining atlas registration informationcomprises transforming an image of the patient to register the image tothe atlas of the population group that is most similar to the patient.16. The system of claim 11, further comprising obtaining user input ofat least one side effect, wherein the scoring of the VOAs also reflectsproduction of the at least one side effect by stimulation of the VOA.17. The system of claim 11, wherein determining the target volumecomprises selecting points for the target volume that belong to athreshold number or percentage of the VOAs.
 18. The system of claim 11,wherein determining the target volume comprises selecting points for thetarget volume that have a threshold score based on the VOAs containingthe point weighted by the scoring of the VOA.